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Transcription factor Sp1

Transcription factor Sp1 is a ubiquitously expressed zinc finger protein encoded by the human SP1 gene (Gene ID: 6667) located on chromosome 12q13.13, consisting of 785 amino acids that form a 100- to 110-kDa nuclear transcription factor essential for regulating thousands of genes involved in fundamental cellular processes such as growth, differentiation, apoptosis, and stress responses.^[1]^[2] It features three C₂H₂-type zinc fingers near the C-terminus that specifically bind GC-rich motifs, such as the consensus sequence 5'-G/TGGGCGG G/A G/A C/T-3', in promoter regions to recruit the basal transcription machinery, including TFIID and TBP, thereby activating or repressing transcription.^[2]^[3] First identified in 1983 through studies of the SV40 virus promoter and cloned in 1987, Sp1 serves as a prototype for constitutive regulators of housekeeping genes while also enabling tissue-specific expression through cooperative interactions with other factors.^[3]^[4] As a member of the 26-member Sp/KLF family of transcription factors, Sp1's activity is dynamically modulated by post-translational modifications, including phosphorylation at over 60 sites (primarily serines and threonines) by kinases like CDK1, MAPK/ERK, and PKC, which influence its DNA-binding affinity, subcellular localization, and interactions with co-regulators such as p300/CBP for histone acetylation or HDAC1 for repression.^[2]^[3] These modifications allow Sp1 to respond to cellular signals, integrating inputs from pathways like cell cycle progression and inflammation to fine-tune gene expression; for instance, it upregulates genes critical for DNA synthesis (e.g., DHFR, TK) and angiogenesis (e.g., VEGF).^[2] In pathological contexts, dysregulated Sp1 contributes to oncogenesis across cancers including colorectal, breast, and prostate by promoting proliferation and metastasis via targets like COX2 and survivin, while its inhibition induces apoptosis, positioning it as a therapeutic target; additionally, elevated Sp1 activity is linked to neurodegenerative diseases like Alzheimer's through regulation of BACE1 and amyloid-beta production.^[5]^[3]

Introduction

Discovery and History

The transcription factor Sp1 was first discovered in 1983 by Robert Tjian and William S. Dynan in extracts from HeLa cell nuclei, where it was identified as a promoter-specific factor that binds to GC-rich motifs, termed GC boxes, in the upstream region of the SV40 virus early promoter. This binding was demonstrated to be essential for accurate and efficient transcription initiation by RNA polymerase II, particularly in the context of viral promoters like SV40.^[6] Sp1 earned its name, Specificity Protein 1, from its sequence-specific affinity for GC- and GT-rich DNA motifs, distinguishing it from other general transcription factors during its purification via DNA affinity chromatography. In 1987, Joseph T. Kadonaga and colleagues cloned a cDNA encoding the C-terminal 696 amino acids of human Sp1, revealing three tandem C2H2-type zinc finger domains responsible for DNA binding; this marked Sp1 as the first eukaryotic transcription factor identified with such a zinc finger structure.^[4] Research in the 1990s solidified Sp1's role in basal transcription of housekeeping genes, which maintain constitutive expression for essential cellular functions like metabolism and proliferation.^[7] By the 2000s, studies expanded to uncover Sp1's involvement in embryonic development—evidenced by lethality in Sp1 knockout mice—and its dysregulation in diseases such as cancer, where it promotes oncogenic gene expression.^[8] The human SP1 gene, located on chromosome 12q13.13, exhibits strong evolutionary conservation across mammals, reflecting its fundamental regulatory functions.^[1]

General Characteristics

Sp1 is a ubiquitously expressed transcription factor encoded by the human SP1 gene located on chromosome 12q13.13, which spans approximately 36 kb and comprises 7 exons. The gene produces a protein consisting of 785 amino acids with a calculated molecular weight of approximately 81 kDa, though it typically migrates at 100-110 kDa on SDS-PAGE due to post-translational modifications.^[1]^[9]^[10] In mammalian cells, Sp1 is predominantly localized in the nucleus and maintains constitutive activity as a basal transcription factor essential for maintaining cellular homeostasis. Its expression is widespread across tissues, with higher levels observed in proliferating cells and embryonic tissues, while lower levels are typical in differentiated and quiescent cells.^[3] Functionally, Sp1 acts as a sequence-specific activator, particularly for TATA-less promoters, playing a critical role in the basal transcription of housekeeping genes and a broad array of others involved in diverse cellular processes. As the prototypical member of the Sp/KLF family, Sp1 exemplifies C2H2 zinc finger proteins, featuring motifs that enable its regulatory functions.^[3]^[7]^[9]

Molecular Structure

Protein Domains

The transcription factor Sp1 possesses a modular protein architecture, with an N-terminal region dedicated to transcriptional activation, a central regulatory domain, and a C-terminal DNA-binding domain. This organization allows for specific interactions with other proteins and DNA, while approximately half of the Sp1 sequence comprises intrinsically disordered regions that confer structural flexibility essential for dynamic binding and regulation.^[7]^[11] The N-terminal transactivation domains (TADs) of Sp1 include three glutamine-rich regions, labeled A, B, and C, which collectively span the activation module. Domains A and B are particularly enriched in glutamine residues (over 25% in these segments) and are interspersed with serine/threonine-rich stretches, facilitating the recruitment of co-activators such as components of the TFIID complex. Domain C, while also glutamine-rich, contains a higher proportion of charged amino acids, contributing to the overall activation potential. These TADs enable Sp1 to stimulate transcription through protein-protein interactions with the basal machinery.^[12] Positioned centrally between the TADs and the DNA-binding domain is an inhibitory domain characterized by a serine/threonine-rich composition, which can suppress transactivation by associating with co-repressors and thereby fine-tuning Sp1's activity levels.^[13] The C-terminal DNA-binding domain features three tandem C₂H₂ zinc finger motifs (ZnF1, ZnF2, and ZnF3), each comprising approximately 28 amino acids and following the consensus sequence Cys-X₂₋₄-Cys-X₁₂-His-X₃₋₅-His. In each motif, two conserved cysteines and two histidines coordinate a single Zn²⁺ ion, stabilizing the characteristic ββα fold observed in nuclear magnetic resonance (NMR) structures of these domains.^[14]^[15] The zinc finger region spans about 81 amino acids in total and represents the most structured portion of Sp1.^[11] The zinc finger domains of Sp1 exhibit high sequence conservation across vertebrate species, with greater than 90% identity among mammals, underscoring their critical role in DNA recognition.^[3]

DNA-Binding Properties

Sp1 primarily recognizes and binds to the GC box, a DNA motif with the consensus sequence 5'-GGGGCGGGGC-3', located in promoter regions approximately 900 to 50 base pairs upstream of the transcription start site. This binding is mediated by the three C-terminal zinc finger domains of Sp1, which insert into the major groove of the DNA helix. Sp1 also interacts with GT box variants, such as 5'-GGTGTGGGG-3', allowing recognition of a broader range of GC-rich sequences.^[16]^[17]^[18] The binding affinity of Sp1 to a single consensus GC box is high, with a dissociation constant (Kd) in the range of 4.1 × 10^{-10} M to 5.3 × 10^{-10} M, as determined by footprinting and gel mobility shift assays. This affinity is enhanced through cooperative interactions when multiple GC boxes are present in tandem arrays, where the C-terminal domain facilitates protein-protein contacts between adjacent Sp1 molecules, leading to DNA bending and increased stability. Mutations in the central GC base pair significantly reduce binding strength, underscoring the role of specific hydrogen bonds in sequence readout.^[16]^[19]^[20] Structural studies using NMR have revealed that the three zinc fingers of Sp1 adopt ββα folds, with fingers 2 and 3 making primary contacts in the major groove via key residues such as arginine and histidine at positions -1, 2, 3, and 6 of the recognition helices. These residues form hydrogen bonds with guanine and cytosine bases, enabling base-specific recognition. Finger 1 contributes less to specificity, allowing Sp1 flexibility in binding diverse motifs while maintaining overall affinity. X-ray crystallography further supports this model, showing zinc finger insertion that distorts the DNA helix for optimal fit.^[21]^[22] Sp1 preferentially binds to TATA-less promoters enriched in CpG islands, where multiple GC boxes enable synergistic occupancy and recruitment of the basal transcription machinery. This context is common in housekeeping and growth-related genes, highlighting Sp1's role in constitutive expression.^[23]^[24]

Transcriptional Function

Mechanism of Gene Regulation

Sp1 regulates gene transcription primarily as an activator by binding to GC-rich motifs, such as GC boxes, in promoter and enhancer regions, thereby facilitating the recruitment of the basal transcription machinery. Through its glutamine-rich transactivation domains (TADs), Sp1 interacts directly with components of TFIID, including TBP and TAFs like hTAFII130, to stabilize the pre-initiation complex (PIC) and promote the assembly of RNA polymerase II holoenzyme.^[3] This bridging function connects enhancer-bound Sp1 to proximal promoter elements, enhancing transcription initiation for both TATA-containing and TATA-less promoters.^[2] In addition to PIC stabilization, Sp1 integrates co-activators to modify chromatin structure, enabling efficient transcription elongation. Sp1 physically associates with histone acetyltransferases (HATs) such as p300/CBP, which catalyze acetylation of histones, including the deposition of H3K27ac marks that maintain an open, permissive chromatin conformation.^[25] These interactions not only increase Sp1's DNA-binding affinity but also counteract repressive chromatin states, allowing access to transcriptional machinery.^[3] Sp1 employs both direct and indirect modes of activation, with the latter involving DNA looping to juxtapose distant enhancers and promoters. In direct activation, proximal Sp1 binding enhances PIC formation, while indirect activation occurs via multimerization of Sp1 molecules that form stable DNA loops, amplifying synergistic effects—up to 78-fold in cases with multiple sites.^[3] Kinetic analyses reveal that Sp1 binding typically induces 4- to 30-fold increases in transcription rates, primarily by elevating the equilibrium constant for PIC assembly and accelerating promoter clearance in a three-step initiation model.^[26] ^[27] Although predominantly activating, Sp1 can repress transcription through competitive binding that displaces other activators or by recruiting repressive complexes like HDAC1.^[3] Its regulatory output is highly context-dependent, favoring activation in GC-rich promoter environments typical of housekeeping genes, but shifting toward repression under conditions such as sumoylation, which alters chromatin interactions and reduces co-activator engagement.^[2]

Key Target Genes

Sp1 regulates a diverse array of target genes across various cellular processes, with chromatin immunoprecipitation followed by sequencing (ChIP-seq) studies identifying over 12,000 binding sites in the human genome, many of which are associated with approximately 6,000 target genes enriched in pathways related to cell proliferation and growth signaling.^[28]^[29]^[30] Among housekeeping genes, Sp1 constitutively maintains expression of essential genes such as GAPDH and β-actin through binding to GC-rich elements in their promoters, ensuring stable basal transcription in diverse cell types.^[31] In cell cycle regulation, Sp1 promotes G1 phase progression by activating genes like Cyclin D1 and CDK4, while repressing p21 to facilitate proliferation.^[32]^[33]^[34] Sp1 also drives expression of growth factor genes, including VEGF to support angiogenesis and TGF-β to modulate signaling pathways involved in cellular responses.^[35]^[36] In viral contexts, Sp1 binding sites in the HIV-1 long terminal repeat (LTR) and the cytomegalovirus (CMV) immediate-early promoter enhance viral gene transcription and replication.^[37]^[38] Recent studies as of 2024 have highlighted Sp1's involvement in liquid-liquid phase separation to activate specific targets like RGS20 in lung adenocarcinoma, underscoring its dynamic regulatory roles.^[39]

Regulation of Sp1

Post-Translational Modifications

Post-translational modifications (PTMs) of the transcription factor Sp1 play a central role in regulating its transcriptional activity, subcellular localization, stability, and interactions with DNA and cofactors. These modifications, including phosphorylation, acetylation, sumoylation, ubiquitination, and glycosylation, occur primarily on residues within the transactivation domains (TADs) and zinc finger regions, allowing fine-tuned control of Sp1 function in response to cellular signals such as growth factors, stress, and metabolic cues. Phosphorylation is one of the most extensively studied PTMs of Sp1, involving multiple kinases that target serine (Ser) and threonine (Thr) residues, particularly in the TADs. Key kinases include mitogen-activated protein kinases (MAPKs) such as ERK, which phosphorylate sites like Thr453 and Thr739, enhancing Sp1's transcriptional activation approximately 2-fold on promoters such as VEGF. Casein kinase 2 (CK2) phosphorylates sites including Thr579, which can modulate DNA binding, though effects vary by context—often reducing binding in some cases while promoting activity in others. Overall, in addition to over 60 putative phosphorylation sites, Sp1 harbors approximately 23 experimentally identified phosphorylation sites, with MAPK/CK2-mediated modifications generally increasing activity during mitogenic stimulation and cell cycle progression, as demonstrated by a 50% reduction in transcriptional output upon mutation of Thr453/Thr739.^[2]^[40]^[41] Acetylation of Sp1 occurs on lysine (Lys) residues in the TADs, primarily mediated by the histone acetyltransferase p300, which targets sites such as Lys703 and Lys704 to promote nuclear retention and recruitment of co-activators like p300 itself. This modification enhances Sp1 stability and transcriptional potency, facilitating gene expression in processes like vascular calcification and cancer progression. Deacetylation by HDACs, such as HDAC1 or HDAC10, counteracts these effects, leading to reduced nuclear localization and activity; for instance, the Sp1-K704A mutant exhibits decreased expression of calcification markers like BMP2.^[42]^[41] Sumoylation involves the covalent attachment of SUMO-1 to Sp1, often at Lys residues, which can shift its function from activation to repression of target genes. Enzymes like PIASy act as E3 ligases to promote this modification, while desumoylation by SENP1 reverses it, reactivating Sp1's transactivation potential. Although specific sites vary, sumoylation generally increases Sp1 stability and nuclear localization but represses activity on select promoters, as seen in enhanced SERCA2a expression during heart failure recovery upon PI3K/Akt-mediated sumoylation. In cancer contexts, regulators like RNF4 and SENP3 further modulate this PTM to influence proliferation and drug resistance.^[42]^[41] Ubiquitination targets Sp1 for proteasomal degradation, primarily through E3 ligases such as the SCF complex involving β-TrCP, TRIM25 (at Lys610), and NEDD4L (at Lys685), marking polyubiquitin chains on Lys residues in the TADs. This process regulates Sp1 turnover, with a half-life of approximately 2-4 hours in cycling cells, preventing excessive accumulation and maintaining balanced transcriptional output. Inhibition of ubiquitination, such as by USP7 deubiquitination, stabilizes Sp1 and promotes angiogenesis in cardiovascular diseases.^[41]^[42] Glycosylation of Sp1, specifically O-linked N-acetylglucosamine (O-GlcNAc) modification, occurs on Ser/Thr residues and is catalyzed by O-GlcNAc transferase (OGT) in response to elevated glucose levels. This PTM modulates Sp1 stability and nuclear localization, enhancing survival in glucose-rich environments like hyperglycemia-associated conditions, though it can also inhibit transcriptional activity on certain promoters such as Ndufa9 in diabetic cardiomyopathy. High glucose induces O-GlcNAcylation, which correlates with increased Sp1-mediated proliferation in breast cancer cells, while removal by O-GlcNAcase (OGA) restores baseline function.^[42]^[43]

Inhibitors and Modulators

Small molecule inhibitors of Sp1 primarily target its DNA-binding activity by competing for GC-rich sequences in promoter regions. Mithramycin A (also known as plicamycin), a prototypical aureolic acid antibiotic, binds selectively to GC boxes, preventing Sp1 from interacting with DNA and thereby inhibiting its transcriptional activation; this disruption occurs with an IC50 of approximately 10 nM in cellular assays measuring Sp1-dependent gene expression.^[44] Other bisanthracyclines, such as WP631, similarly block Sp1 binding to consensus sites, leading to selective suppression of Sp1-driven transcription in vitro.^[45] Peptide-based inhibitors have emerged as tools to disrupt Sp1's interactions with co-activators by mimicking its transactivation domains (TADs). These synthetic peptides, often designed as α-helical mimetics, interfere with the recruitment of co-factors like TBP-associated factors, thereby attenuating Sp1-mediated gene activation without affecting DNA binding directly.^[46] Natural modulators, such as betulinic acid, promote Sp1 degradation through the ubiquitin-proteasome pathway, reducing its protein levels and downstream transcriptional effects. This triterpenoid compound enhances ubiquitination of Sp1, leading to its proteasomal breakdown in cancer cells, as observed in prostate and other tumor models.^[47] Endogenous inhibitors include the related transcription factor Sp3, which acts as a competitive antagonist by binding to the same GC-rich motifs as Sp1 but functioning as a repressive isoform to dampen activation.^[48] Additionally, the miR-29 family of microRNAs downregulates Sp1 expression post-transcriptionally by targeting its mRNA, resulting in reduced Sp1 protein levels and altered gene regulation in various cellular contexts.^[49] Among clinical candidates, the liver X receptor (LXR) agonist TO901317 indirectly inhibits Sp1 activity by altering its phosphorylation status, which diminishes DNA-binding affinity and transcriptional potency.^[42] Recent studies from 2023 to 2025 have explored Sp1 inhibitors, including mithramycin analogs, for potential advancement into clinical trials for cancer, focusing on their ability to modulate tumor microenvironments.^[50]

Protein Interactions

Physical Binding Partners

Sp1, a zinc finger transcription factor, engages in direct protein-protein interactions with various co-activators, corepressors, and signaling partners to modulate its activity at target gene promoters. These interactions primarily occur through specific domains such as the transactivation domains (TADs), glutamine-rich regions, and zinc finger DNA-binding domains (ZnFs) of Sp1. High-throughput methods like yeast two-hybrid (Y2H) screening and co-immunoprecipitation (co-IP) have identified numerous physical binding partners for Sp1, with a significant enrichment in components of the transcription initiation machinery, including TFIID subunits and histone-modifying enzymes.^[3] Among co-activators, Sp1 interacts with p300/CBP histone acetyltransferases, where the KIX domain of p300/CBP binds to Sp1's TAD B, facilitating recruitment to chromatin and enhancement of transcriptional activation; this interaction is strengthened by ATM-mediated phosphorylation of Sp1 at DNA double-strand breaks.^[51] Additionally, Sp1 binds TAF4 and TAF9 within the TFIID complex via its glutamine-rich activation domains, promoting stable association with core promoters and bridging to RNA polymerase II; structural studies show TAF4's Q-rich domains forming disordered interactions with Sp1, while TAF9 contributes to overall complex stability.^[52]^[53] Corepressors such as HDAC1 and HDAC2 physically associate with Sp1 through its C-terminal inhibitory domain and ZnF regions, leading to deacetylation of histones and repression of target genes; co-IP experiments confirm HDAC1/2 recruitment to Sp1-bound promoters in multimeric complexes.^[54] Sp1 also forms heterodimers with Sp3 via homologous ZnF domains, allowing competitive or cooperative binding to GC-rich motifs, as demonstrated by Y2H and co-IP assays showing direct interaction independent of DNA.^[3] Signaling partners include STAT3, which binds Sp1's TAD through its SH2 domain, enabling crosstalk in cytokine-responsive gene regulation; immunoprecipitation studies in confluent cells verify this physical contact, influencing nuclear localization and stability.^[55] Similarly, NF-κB p65 interacts with Sp1's ZnF domains via the Rel homology domain of p65, promoting synergistic DNA binding at adjacent κB and GC-box sites, as evidenced by in vitro pull-down and co-IP experiments.^[56]

Functional Interactions

Sp1 exhibits synergy with the AP-1 transcription factor in the MAPK/ERK signaling pathway, particularly in regulating genes associated with cell proliferation, such as CCND1 encoding cyclin D1.^[57] The ERK pathway activates AP-1 complexes, which cooperate with Sp1 to enhance transcriptional activation of these proliferation-related targets.^[58] Additionally, Sp1 participates in cooperative chromatin looping with CTCF to facilitate enhancer-promoter contacts, thereby integrating distant regulatory elements for efficient gene expression.^[59] In Wnt/β-catenin signaling, Sp1 engages in crosstalk by being recruited to sites bound by TCF transcription factors, where it stabilizes β-catenin and amplifies target gene transcription.^[60] This recruitment enhances the pathway's output without direct binding to canonical Wnt response elements. Sp1 cooperates with p53 in the regulation of apoptosis, enhancing p53-dependent activation of pro-apoptotic genes and supporting cell death pathways.^[61] ChIP-seq analyses have elucidated the dynamic binding of Sp1 at promoters and enhancers, revealing its role as a central hub in transcriptional networks.^[62] Sp1 connects to a significant portion of cancer-related pathways, including PI3K/AKT, which influences cell survival and metabolism; for instance, Sp1 modulates PI3K/AKT signaling through regulation of downstream effectors, integrating it into broader oncogenic networks.^[63] Sp1's interactions display dynamic shifts across the cell cycle, with cyclin-dependent kinases such as cyclin A-CDK2 phosphorylating Sp1 during G1/S transition to enhance its transcriptional activity on cell cycle genes.^[64] These modifications alter Sp1's partner associations, adapting its function to phase-specific regulatory needs.

Biological Roles

In Normal Physiology

Sp1 plays a pivotal role in cell proliferation and differentiation, particularly during early embryonic development. Targeted disruption of the Sp1 gene in mice results in embryonic lethality around day 10.5, characterized by severe growth retardation, thin yolk sacs, and widespread apoptosis, underscoring its indispensability for proper embryogenesis. This lethality arises from defective chorio-allantoic fusion and impaired mesodermal development, with embryos accumulating undifferentiated ectoderm-like tissue. Furthermore, Sp1 supports the maintenance of embryonic stem cell pluripotency by binding to Sp1/Sp3 sites in the promoter of Nanog, a core transcription factor that sustains the undifferentiated state.^[65] In metabolic homeostasis, Sp1 regulates key genes involved in glucose handling and energy balance. It facilitates the transcription of the insulin gene in pancreatic beta cells by binding to GC-rich elements in the promoter, where its activity is modulated by glucose levels to ensure appropriate insulin secretion for glycemic control.^[66] Sp1 also governs insulin-like growth factor 1 (IGF1) gene expression through interactions with downstream regulatory regions, contributing to systemic growth and metabolic signaling. In adipose tissue, Sp1 cooperates with peroxisome proliferator-activated receptor gamma (PPARγ) to drive adipocyte differentiation, enhancing the expression of genes like GLUT4 for glucose uptake and supporting lipid storage and insulin sensitivity.^[67]^[68] Sp1 contributes to genomic integrity by activating nucleotide excision repair (NER) pathways in response to DNA damage. Following ultraviolet (UV) exposure, Sp1 binds to the promoter of XPC, a critical NER component that recognizes bulky DNA lesions, thereby promoting repair fidelity and preventing mutagenesis. This transcriptional activation helps maintain cellular homeostasis under genotoxic stress, with reduced Sp1 binding observed in UV-irradiated cells leading to impaired XPC expression.^[69] In immune regulation, Sp1 ensures constitutive expression of major histocompatibility complex (MHC) class I molecules, which are essential for antigen presentation and immune surveillance. By occupying core promoter elements, including Sp1 binding sites, Sp1 sustains basal MHC class I transcription across cell types, facilitating CD8+ T cell recognition of self and foreign peptides.^[70] Sp1 also supports basal expression of cytokine genes, such as interleukin-6 (IL-6), through binding to multiple GC boxes in the promoter, providing a foundation for innate immune responses and inflammation resolution.^[71] Sp1 exerts conserved functions in developmental processes, including organogenesis and tissue invasion. During placentation, Sp1 promotes trophoblast invasion by upregulating matrix metalloproteinase 2 (MMP2) expression, enabling extracellular matrix remodeling essential for implantation and spiral artery transformation. In organogenesis, Sp1 regulates genes like Bmp7 in embryonic kidney development via NFAT2/Sp1 interactions, influencing branching morphogenesis and glomerular formation. Its broad involvement in these processes highlights a conserved role across vertebrate development, as evidenced by the early embryonic lethality in Sp1-deficient models.^[72]^[73]

In Disease Pathogenesis

Sp1 overexpression is frequently observed in various solid tumors, including breast and prostate cancers, where it contributes to oncogenic progression by dysregulating multiple downstream targets.^[50]^[74] In these malignancies, elevated Sp1 levels promote tumor cell proliferation, invasion, and metastasis through transcriptional activation of pro-angiogenic and extracellular matrix-degrading genes such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9).^[75]^[76] For instance, Sp1 binding to GC-rich motifs in the VEGF promoter enhances vascularization, facilitating nutrient supply to hypoxic tumor regions, while its regulation of MMP9 expression enables basement membrane degradation, thereby supporting epithelial-to-mesenchymal transition and distant dissemination.^[75]^[76] This aberrant Sp1 activity often correlates with poor prognosis and advanced disease stages in breast and prostate cancers.^[50] In cardiovascular diseases, Sp1 upregulation plays a key role in pathological vascular remodeling during atherosclerosis, primarily through interactions with platelet-derived growth factor (PDGF) signaling. PDGF stimulation in vascular smooth muscle cells enhances Sp1 binding to target promoters, leading to increased expression of genes involved in cell proliferation and migration that contribute to plaque formation and instability.^[77] A 2024 review highlights Sp1's involvement in cardiac hypertrophy, where it cooperates with factors like GATA4 to regulate atrial natriuretic factor (ANF) expression, exacerbating cardiomyocyte enlargement and fibrosis in response to hypertrophic stimuli.^[78] This dysregulation promotes maladaptive ventricular remodeling and systolic dysfunction in hypertensive or ischemic hearts.^[78] In neurodegeneration, particularly Alzheimer's disease, Sp1 hyperactivation drives amyloid-β pathology by enhancing transcription of the amyloid precursor protein (APP) gene. Sp1, often in cooperation with Smad proteins under TGF-β influence, binds to the APP promoter to increase APP mRNA and protein levels, thereby elevating amyloid-β production and plaque accumulation in neuronal cells.^[79] This mechanism contributes to synaptic dysfunction and neuroinflammation, accelerating cognitive decline in affected individuals.^[79] Sp1 facilitates viral pathogenesis in infections, notably by binding to GC boxes in retroviral long terminal repeat (LTR) promoters to support transcriptional activation. A 2025 review details Sp1's role in enhancing promoter activity across human retroviruses, including HIV-1, where it aids in reversing latency by boosting viral gene expression upon cellular activation signals.^[80] In HIV, Sp1 sites in the LTR are critical for basal and induced transcription, and their modulation can promote latency reversal, potentially complicating viral persistence in reservoirs.^[80] In metabolic disorders like diabetes, Sp1 mediates hyperglycemia-induced renal fibrosis through synergistic upregulation of transforming growth factor-β (TGF-β) signaling. High glucose environments increase Sp1 and c-Jun expression in renal mesangial cells, which bind cooperatively to the TGF-β1 promoter, elevating TGF-β1 levels and subsequent extracellular matrix deposition via collagen synthesis.^[81] This pathway drives glomerular and tubular fibrosis, contributing to diabetic nephropathy progression and end-stage renal disease.^[81]

Therapeutic Implications

Targeting in Cancer

Strategies targeting the transcription factor Sp1 have emerged as promising anticancer approaches due to its frequent overexpression in tumors and role in driving oncogene expression. Inhibitor classes include GC-box antagonists, which disrupt Sp1's DNA-binding affinity to GC-rich motifs in promoter regions. For instance, distamycin derivatives bind the minor groove of DNA, displacing Sp1 from its binding sites and selectively inhibiting transcription of Sp1-dependent genes in cancer cells. Additionally, Sp1 degradation inducers promote proteasomal breakdown of the protein, reducing its stability and activity. Thiazolidinedione derivatives, such as OSU-CG12, facilitate ubiquitination and degradation of Sp1 in prostate cancer models, mimicking glucose deprivation effects to suppress tumor progression. Combination therapies leveraging Sp1 inhibition with other agents show synergistic effects in repressing key oncogenic targets. Histone deacetylase (HDAC) inhibitors like vorinostat downregulate Sp1 expression by altering chromatin structure and interfering with Sp1-mediated transcription, while also reducing levels of Sp1-regulated anti-apoptotic proteins such as survivin. In rhabdomyosarcoma and other solid tumors, vorinostat combined with Sp1 antagonists enhances apoptosis and inhibits cell proliferation more effectively than monotherapy, as the dual repression of survivin disrupts survival pathways in cancer cells. Clinical progress includes evaluation of mithramycin analogs, which potently inhibit Sp1 by binding GC-rich DNA sequences. EC-8042, a mithramycin derivative, has demonstrated preclinical efficacy in ERG-positive prostate cancer xenografts by reprogramming transcription and inhibiting tumor angiogenesis, supporting its advancement to clinical testing. Nanoparticle-based delivery systems improve specificity and reduce toxicity for such agents, enabling targeted accumulation in tumor tissues. Earlier trials, such as phase II studies of mithramycin in advanced cancers including prostate, reported antitumor activity linked to Sp1 suppression, though updates emphasize analogs for better pharmacokinetics. Sp1 levels serve as a prognostic biomarker in colorectal cancer (CRC), where elevated expression correlates with advanced stage, lymph node metastasis, and poor overall survival. Meta-analyses indicate that high Sp1 is associated with unfavorable outcomes across gastrointestinal cancers. Resistance to Sp1-targeted therapies can arise from mutant Sp1 variants that evade inhibitor binding or through compensatory upregulation of paralogs like Sp3, which maintain transcription of shared oncogenic targets. Recent 2024 studies highlight post-translational modifications, such as phosphorylation at S101, enabling Sp1 persistence in temozolomide-resistant gliomas, while Sp1/Sp3 redundancy contributes to therapy escape in multiple cancers. As of 2025, ongoing research underscores Sp1's role in colorectal and pancreatic cancer progression, suggesting enhanced potential for targeted inhibitors in combination therapies.^[50]

Applications in Other Diseases

In cardiovascular diseases, modulation of Sp1 has shown promise for alleviating hypertension and associated cardiac fibrosis. Endothelial-specific deficiency of Sp1 and Sp3 leads to elevated blood pressure, impaired vasodilation, and cardiac hypertrophy, underscoring Sp1's role in vascular homeostasis and its potential as a therapeutic target.^[82] A 2024 review highlights that Sp1 knockdown reduces myocardial fibrosis by disrupting pathways such as TGF-β/Smad3 and NF-κB/miR-29, thereby mitigating inflammation and extracellular matrix deposition in hypertensive models.^[78] Similarly, inactivation of Sp1 via miR-7a/b overexpression attenuates fibroblast proliferation and fibrosis post-myocardial infarction, suggesting RNA-based interventions as viable strategies.^[78] In infectious diseases, particularly herpes simplex virus type 1 (HSV-1), Sp1 interacts with the glucocorticoid receptor (GR) to facilitate viral reactivation and replication, presenting opportunities for antiviral therapies. Activation of GR by glucocorticoids enhances Sp1 binding to HSV-1 immediate early promoters, promoting gene expression and explant-induced reactivation from latency in preclinical models.^[83] This GR-Sp1 axis also boosts HSV-1 replication under stress conditions, indicating that antagonists targeting Sp1 or GR-Sp1 interactions could suppress viral activity, as demonstrated in cell culture studies where GR inhibition reduced viral yields.^[84] For cytomegalovirus (CMV), Sp1 contributes to major immediate early promoter activity, and competitive inhibition by factors like CREB1 has been shown to block CMV transcription and replication, supporting Sp1 as a target for broad-spectrum antivirals.^[85] Sp1 modulation holds therapeutic relevance in metabolic disorders such as obesity, where it influences adipogenesis. During adipogenic differentiation of adipose-derived stem cells, Sp1 activation, enhanced by miR-29b upregulation, inhibits TNF-α signaling to promote fat cell formation, highlighting Sp1's pro-adipogenic role.^[86] In obesity models, this pathway contributes to excessive lipid accumulation, and targeted Sp1 inhibitors could potentially regulate adipocyte differentiation to counter metabolic imbalance, though clinical translation remains exploratory. In neuroprotection for Parkinson's disease (PD), suppressing Sp1 via microRNA therapeutics emerges as a strategy to mitigate neurodegeneration. miR-29c, downregulated in PD patients, targets Sp1 to reduce inflammation, apoptosis, and α-synuclein aggregation in dopaminergic neurons, as evidenced in MPTP-induced mouse models where miR-29c overexpression preserved substantia nigra integrity and lowered pro-inflammatory cytokines like TNF-α and IL-6.^[87] This suppression alleviates microglial activation and NLRP3 inflammasome activity, offering preclinical evidence for miRNA-based interventions to slow PD progression.^[88] For autoimmunity, particularly systemic lupus erythematosus (SLE), Sp1 contributes to disease pathogenesis through IFN-α regulation, with implications for targeted therapies. In childhood-onset SLE, elevated Sp1 mRNA correlates with increased IRF5 and IFN-α expression, driving type I interferon production and proinflammatory responses via Sp1 binding to the IRF5 promoter.^[89] Histone deacetylase inhibitors like trichostatin A repress Sp1 activity on the IRF5 promoter, reducing IFN-α, TNF-α, and IL-6 levels in SLE models, suggesting epigenetic modulation of Sp1 as a potential treatment avenue to dampen autoimmune inflammation.^[89]

References

[1]
6667 - Gene ResultSP1 Sp1 transcription factor [ (human)] - NCBI
Sep 14, 2025 · The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promoters.
[2]
Sp1 Phosphorylation and Its Regulation of Gene Transcription - NIH
Sp1 is a 785-amino-acid, 100- to 110-kDa nuclear transcription factor which regulates gene expression via multiple mechanisms.
[3]
The Role of the Ubiquitously Expressed Transcription Factor Sp1 in ...
Dec 23, 2016 · Sp1 functions by recruiting the basal transcription machinery and, specifically, interacting with members of the TFiiD complex. TFiiD is ...
[4]
Isolation of cDNA encoding transcription factor Sp1 and functional ...
Transcription factor Sp1 is a protein present in mammalian cells that binds to GC box promoter elements and selectively activates mRNA synthesis.
[5]
Transcription Factor Sp1 - an overview | ScienceDirect Topics
The Sp1 transcription factor is a mediator of critical physiological pathways including cell cycle, proliferation, and metastasis.
[6]
The promoter-specific transcription factor Sp1 binds to ... - PubMed
These results suggest that direct binding of Sp 1 to sequences in the upstream promoter element is the mechanism by which this factor activates transcription.
[7]
Sp1 and the 'hallmarks of cancer' - Beishline - 2015 - FEBS Press
Nov 13, 2014 · Initially, Sp1 was considered a general transcription factor that is required for transcription of a large number of 'housekeeping genes', so- ...
[8]
Transcription factor Sp1 - Homo sapiens (Human) - UniProt
Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich ...Missing: cloning | Show results with:cloning
[9]
Gene: SP1 (ENSG00000185591) - Summary - Ensembl
Sp1 transcription factor [Source:HGNC Symbol;Acc:HGNC:11205]. Location. Chromosome 12: 53,380,176-53,416,446 forward strand. GRCh38:CM000674.2.
[10]
Sp1- and Krüppel-like transcription factors | Genome Biology | Full Text
Feb 3, 2003 · Sp1-like proteins and Krüppel-like factors (KLFs) are highly related zinc-finger proteins that are important components of the eukaryotic cellular ...
[11]
Studying the recruitment of Sp1 to the β-globin promoter with ... - PNAS
The structure of the Sp1 pointer ABCZD (16) is shown at the bottom. Domains A and B contain serine/threonine- and glutamine-rich regions, interact with TATA ...Missing: transactivation | Show results with:transactivation
[12]
Transcriptional activity of Sp1 is regulated by molecular interactions ...
Sp1 is composed of several functional domains, such as the inhibitory domain (ID), two serine/threonine-rich domains, two glutamine-rich domains, three C2H2- ...Missing: review | Show results with:review
[13]
Structures of zinc finger domains from transcription factor Sp1 ...
Mar 21, 1997 · The carboxyl terminus of transcription factor Sp1 contains three contiguous Cys2-His2 zinc finger domains with the consensus sequence Cys-X2-4-Cys-X12-His-X3- ...Missing: crystal 1ZGC
[14]
Measurement of the binding of transcription factor Sp1 to a single ...
The equilibrium constant was determined for the binding of the transcription factor Sp1 to a single consensus GC box DNA recognition site, (5'-GGGGCGGGGC-3').
[15]
Cloning of GT box-binding proteins: a novel Sp1 multigene family ...
These GT box-binding proteins were identified as members of a novel Sp1 multigene family. Two of them, which we term Sp2 and Sp3, were cloned.Missing: 1988 | Show results with:1988
[16]
The binding of the ubiquitous transcription factor Sp1 at the locus ...
Our results suggest that Sp1 is an inhibitor of β-like globin gene transcription during erythroid terminal differentiation.Missing: characteristics mammalian
[17]
The Role of Sp1 Family Members, the Proximal GC-Rich Motifs, and ...
Finally, the C-terminal domain D is important for cooperative interactions among Sp1 molecules when bound to promoters containing multiple GC boxes ( 30). Sp1 ...
[18]
Selected base sequence outside the target binding site of zinc finger ...
In some promoter sequences the GC box is often arranged as a tandemly repeated array and Sp1 binds to such a sequence with cooperative bending of the DNA (8,10) ...
[19]
NMR structure of transcription factor Sp1 DNA binding domain
Dec 28, 2004 · The DNA-binding domain of Sp1 consists of three Cys(2)His(2)-type zinc finger motifs. They have typical betabetaalpha zinc finger folds and ...Missing: crystal 1ZGC
[20]
Structures of Zinc Finger Domains from Transcription Factor Sp1
However, Sp1 binds independently to each GC box sequence; physical interaction between adjacent. Sp1 molecules is insufficient to give rise to cooperative DNA.
[21]
CpG islands and the regulation of transcription - PMC
These include the general transcription factor Sp1, which has been shown to recruit TATA-binding protein (TBP) to promoters lacking a TATA box (Butler and ...
[22]
Multiple and Essential Sp1 Binding Sites in the Promoter for ...
The 39-terminal 300-bp sequence encompassing this re- gion contains a GC-rich CpG island, seven consensus Sp1 bind- ing sites, and two CCAAT boxes. Transfection ...
[23]
Diverse Mechanisms of Sp1-Dependent Transcriptional Regulation ...
Sp1 is a ubiquitously-expressed transcription factor that plays a vital role in the regulation of numerous genes required for normal cell function. In addition ...
[24]
Using synthetic bacterial enhancers to reveal a looping-based ...
Feb 2, 2016 · To do so, we modified the wormlike chain model to generate chains made of finite volume links (Supplementary Fig. 1a,b). Such 'thick' chains can ...Simulating Quenching... · Synthetic Enhancers With A... · Indel Mutations In Natural...
[25]
Transcription Activation by GC-Boxes: Evaluation of Kinetic and ...
In this report we study RNA polymerase II transcription activated by Sp1 at GC-boxes and find that the data strongly favor a thermodynamic model. The approach ...
[26]
Kinetic analysis of Sp1-mediated transcriptional activation of a TATA ...
Feb 1, 2000 · A detailed kinetic analysis based on a three-step kinetic model of transcription initiation showed that Sp1 stimulates the activity of the pAS8 ...
[27]
Unbiased Mapping of Transcription Factor Binding Sites along ...
This mapping reveals an unexpectedly large number of transcription factor binding site (TFBS) regions, with a minimal estimate of 12,000 for Sp1, 25,000 for ...
[28]
Identification of novel Sp1 targets involved in proliferation and ...
Aug 6, 2025 · It is documented that more than 12,000 Sp1 binding sites have been found in the human genome [12] . Historically, Sp1 has been regarded as a ...
[29]
Activating elements in the promoter region of the chicken β-actin gene
Transcription factor Sp1 recognizes promoter sequences from the monkey genome that are similar to the simian virus 40 promoter. N. Fregien et al. The LTR of ...
[30]
The elements of human cyclin D1 promoter and regulation involved
Feb 11, 2011 · The transcription factor SP1 is a DNA-binding protein which interacts with a variety of gene promoters containing GC-box elements. Among many ...E2f · Creb/atf2 · Signal Transduction Pathway
[31]
Down-regulation of Sp1 suppresses cell proliferation, clonogenicity ...
Aug 7, 2014 · Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or β-actin was used as an internal control. The primers are listed in Table 2. Relative ...
[32]
Sp1 inhibits proliferation and induces apoptosis in vascular smooth ...
Sp1 inhibits proliferation and induces apoptosis in vascular smooth muscle cells by repressing p21WAF1/Cip1 transcription and cyclin D1-Cdk4-p21WAF1/Cip1 ...
[33]
Sp1 Is Involved in Akt-mediated Induction of VEGF Expression ...
Role of Akt and Sp1 in VEGF promoter activation. In all panels, pSV-β-galactosidase was cotransfected as a control for transfection efficiency along with the ...Akt Regulates Vegf Mrna And... · Sp1 Binding Sites In The... · Akt Increases Binding Of...<|separator|>
[34]
Butyrate produced by gut commensal bacteria activates TGF-beta1 ...
Jun 27, 2018 · Butyrate produced by gut commensal bacteria activates TGF-beta1 expression through the transcription factor SP1 in human intestinal epithelial ...
[35]
Role of SP1-binding domains in in vivo transcriptional regulation of ...
These results suggest that SP1, through its interaction with other DNA-binding proteins, is critical for in vivo transcriptional regulation of HIV.
[36]
Two Sp1/Sp3 Binding Sites in the Major Immediate-Early Proximal ...
Both the Sp1 and Sp3 binding sites have a positive and synergistic effect on the human cytomegalovirus (HCMV) major immediate-early (MIE) promoter. There was ...
[37]
Role of post-translational modifications of Sp1 in cancer
Aug 20, 2024 · Sp1 activity and stability are affected by post-translational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, glycosylation, and ...
[38]
Role of post-translational modifications of Sp1 in cardiovascular ...
Post-translational modifications (PTMs) of Sp1, such as phosphorylation, ubiquitination, acetylation, glycosylation, SUMOylation, and S-sulfhydration, can ...3.2 Acetylation · 3.5 Sumoylation · 3.7. 1 Acetylation And...
[39]
O-linkage of N-acetylglucosamine to Sp1 activation domain inhibits ...
We show that O-GlcNAcylation of a chimeric transcriptional activator containing the second activation domain of Sp1 decreases its transcriptional activity.Missing: Ser/ | Show results with:Ser/
[40]
Mithramycin Is a Gene-Selective Sp1 Inhibitor That Identifies a ... - NIH
Mithramycin is a gene-selective Sp1 inhibitor that identifies a biological intersection between cancer and neurodegeneration.
[41]
Sp1-Targeted Inhibition of Gene Transcription by WP631 in ...
May 18, 2004 · Bisanthracycline WP631, a potent inhibitor of Sp1-activated transcription in vitro, was assayed for its ability to specifically inhibit ...
[42]
Drugging the Undruggable: Transcription Therapy for Cancer - PMC
(C) Peptide mimetics or small molecules disrupt dimerization of transcription factors, or interactions between transcription factors and their co-regulators.2. Transcriptional... · 4.1. Peptide Mimetics And... · 5. Epigenetic Interventions...<|control11|><|separator|>
[43]
Betulinic Acid Inhibits Prostate Cancer Growth through Inhibition of ...
Mar 15, 2007 · Betulinic acid acts as a novel anticancer agent through targeted degradation of Sp proteins that are highly overexpressed in tumors.
[44]
Sp1-mediated transcriptional activation is repressed by Sp3 - PMC
A mutant of Sp3 lacking the DNA binding domain does not affect activation by Sp1, suggesting that the inhibition is most likely due to the competition with Sp1 ...
[45]
miR-29s: a family of epi-miRNAs with therapeutic implications in ...
May 30, 2015 · In MM cells, SP1 acts by repressing miR-29b promoter thus reducing miR-29b expression; miR-29b in turn targets SP1, DNMT3A and DNMT3B, thus ...
[46]
https://pmc.ncbi.nlm.nih.gov/articles/PMC3529832/
[47]
Sp1-dependent recruitment of the histone acetylase p300 to DSBs ...
Jul 7, 2021 · Specifically, cells depleted of Sp1 display defects in the acetylation of H3K18, resulting in defective SWI/SNF and Ku70 recruitment to DSBs.Missing: Lys TAD nuclear
[48]
Interaction between intrinsically disordered regions in transcription ...
We herein report the structural details of the glutamine‐rich domains (Q‐domains) of Sp1 and TAF4 using circular dichroism (CD) and heteronuclear magnetic ...
[49]
Structures of three distinct activator–TFIID complexes
Using body-labeled Sp1 revealed that TAF1, TAF4, and TAF6 are located within 21 Å of Sp1 bound to TFIID. ... interaction between TAF1 and Sp1 as shown in Figure ...
[50]
Histone Deacetylase 1 Can Repress Transcription by Binding to Sp1
For instance, HDAC1 and HDAC2 were recently shown to interact with each other (22), and both deacetylases are present in Sin3-containing complexes (32, 66, 68).
[51]
Cell confluency-induced Stat3 activation regulates NHE3 expression ...
Immunoprecipitation performed with the nuclear extracts demonstrated physical interaction of Stat3 and Sp1/Sp3 triggered by cell confluency. Stat3 inhibition by ...
[52]
Functional Interference of Sp1 and NF-κB through the Same DNA ...
The ubiquitous transcription factor Sp1 contains a three-zinc-finger DNA binding domain and four transactivation domains (9, 10, 25) and binds to GC-rich sites ...
[53]
Estrogen Receptor Beta (ERβ): A Ligand Activated Tumor Suppressor
Oct 23, 2020 · The cell division protein cyclin D1 (CCND1), one target of AP-1 and SP1 mediated transcription, is upregulated by ERα and induces estrogen- ...Natural Erβ Ligands · Erβ: Genetic Locus, Domain... · Erβ Expression And Role In...
[54]
Epidermal Growth Factor Receptor Cell Proliferation Signaling ...
The ERK pathway induces CYCLIN D1 expression through its activation of the AP-1 complex. Transcriptionally, ERK induces the expression of immediate early genes ...
[55]
Enhancer-promoter interactions are encoded by complex genomic ...
Jun 16, 2016 · Sp1 regulates chromatin looping between an intronic enhancer and distal promoter of the human heme oxygenase-1 gene in renal cells. J Biol ...
[56]
Regulation of Transcription Factor SP1 by the β-Catenin Destruction ...
Here we report that SP1 is a downstream target of the Wnt signaling pathway. We show that β-catenin is required for SP1 stability in a GSK3β-dependent manner.
[57]
The puzzling interplay between p53 and Sp1 - PMC - PubMed Central
May 9, 2017 · Both p53 and Sp1 therefore are central cellular transcription factors, regulating critical cellular life and death decisions.
[58]
Role of Sp Transcription Factors in the Regulation of Cancer Cell ...
Glycolysis and lipogenesis in cancers are also known to be stimulated by the constitutive activation of the PI3K/Akt signaling pathway. Evidence is presented ...
[59]
Different SP1 binding dynamics at individual genomic loci in ... - PNAS
In line with previous reports, 68% of SP1 target sites are in promoter regions, 23% are in enhancer regions, 3.3% are in gene bodies, 4.1% are in Polycomb- ...
[60]
Cyclin A–CDK phosphorylates Sp1 and enhances Sp1‐mediated ...
In eukaryotic cells, cell cycle progression is regulated by the sequential activation of cyclin‐dependent kinases (CDKs). Cyclin A acts in two distinct stages.
[61]
Functional analysis of two Sp1/Sp3 binding sites in murine Nanog ...
Mar 16, 2006 · Supershift experiments showed that addition of Sp1 antibody inhibited the formation of the upper band, and the two bands below were inhibited ...
[62]
Role of Sp1 in insulin regulation of gene expression - PubMed
This review points to an ever-increasing role for Sp1 in regulating the transcription of genes in response to extracellular signals such as insulin.
[63]
Involvement of Sp1 in the transcriptional regulation of the rat insulin ...
Sp1 and related factors may play an important role in the regulation of IGF-I gene transcription, through interactions with region V downstream from the major ...
[64]
Role of Specificity protein-1, PPARgamma, and Pituitary ... - PubMed
May 25, 2004 · ... adipocyte differentiation. Since the transcription factors specificity protein-1 (SP-1) and PPARgamma have been demonstrated to modulate ...
[65]
Protective Effect of Diphlorethohydroxycarmalol against Ultraviolet B ...
Sep 2, 2015 · DPHC restored binding of the SP1 to the XPC promoter, which is reduced in UVB-exposed cells. These results indicate that DPHC can protect cells ...
[66]
Major histocompatibility complex class I core promoter elements are ...
Sep 9, 2013 · Major histocompatibility complex class I genes are ubiquitously expressed and governed by tissue-specific and hormonal signals. Transcription ...
[67]
Binding and functional effects of transcriptional factor Sp1 ... - PubMed
Mar 29, 1996 · In this study we demonstrate that the transcription factor Sp1 binds to these repeats and plays an important role in basal and in inducible ...
[68]
Acetaminophen overdose suppresses human extravillous ... - PubMed
Aug 8, 2025 · Acetaminophen overdose suppresses human extravillous trophoblast invasion by downregulating SP1-mediated MMP2 expression · Abstract · MeSH terms.
[69]
and Sp1-mediated Bmp7 expression - PubMed
Gpr54 regulates Bmp7 expression through NFAT2 and Sp1 and plays an important role in embryonic kidney branching morphogenesis and glomerular development.
[70]
SP1 Expression and the Clinicopathological Features of Tumors
Besides, SP1 binds to the promoter of vascular endothelial growth factor (VEGF) to facilitate angiogenesis, forming a favorable condition for tumor growth [3].
[71]
SP1 promotes tumor angiogenesis and invasion by activating VEGF ...
SP1 promotes tumor angiogenesis and invasion by activating VEGF expression in an acquired trastuzumab‑resistant ovarian cancer model · Authors · Affiliation.
[72]
Matrix metalloproteinases participation in the metastatic process and ...
Multiple GC boxes that bind to specificity protein-1 (Sp1) and Sp3 transcription factors have been identified in their proximal promoters. The MMPs from ...
[73]
Platelet-Derived Growth Factor Enhances Sp1 Binding to the LDL ...
Our data demonstrate that PDGF stimulation of quiescent cells leads to enhanced Sp1 binding to the LDL receptor gene.
[74]
Role of Specificity Protein 1 (SP1) in Cardiovascular Diseases
Jul 7, 2024 · SP1 is a crucial transcription factor that regulates various cellular functions. It plays a significant role in cell growth, differentiation, ...2. Sp1 Gene And Protein... · 4. Sp1 In Cardiac Diseases · 5. Perspective And...
[75]
Co-localization and Distribution of Cerebral APP and SP1 and ... - NIH
Mar 21, 2018 · Sp1 and Smad transcription factors co-operate to mediate TGF-beta-dependent activation of amyloid-beta precursor protein gene transcription.Missing: hyperactivation | Show results with:hyperactivation
[76]
Viral Appropriation of Specificity Protein 1 (Sp1): The Role of Sp1 in ...
In this review, we start by summarizing the relationships between Sp1 function, DNA binding, and structural motifs. We then describe the role Sp1 plays in ...
[77]
Synergistic effects of c-Jun and SP1 in the promotion of TGFβ1 ...
The increase in c-Jun and SP1 expressions was positively correlated with TGFβ1 in both high glucose-treated human renal mesangial cells (HRMCs) and diabetic ...<|control11|><|separator|>
[78]
Endothelial Sp1/Sp3 are essential to the effect of captopril on blood ...
Sep 21, 2023 · These results show that Sp1/Sp3 deficiency in endothelia resulted in elevated blood pressure, impaired vasodilation, and cardiac hypertrophy.Missing: PP2 | Show results with:PP2
[79]
Glucocorticoid receptor and specificity protein 1 (Sp1) or Sp3 ...
Nov 4, 2024 · Glucocorticoid receptor (GR) activation enhances Human alpha-herpes virus 1 (HSV-1) replication and explant-induced reactivation from latency.
[80]
Glucocorticoid receptor and specificity protein 1 (Sp1) or Sp3, but ...
Mar 29, 2024 · Activation of the glucocorticoid receptor (GR) by stressful stimuli enhances HSV-1 gene expression, replication, and explant-induced reactivation.
[81]
Inhibition of human cytomegalovirus replication by overexpression ...
Here we show that overexpression of CREB1 potently blocked MIE transcription and HCMV replication. Surprisingly, CREB1 still exhibited strong inhibition of the ...
[82]
MicroRNA-29b promotes the adipogenic differentiation of human ...
Results: During the normal adipogenic differentiation of ADSCs, up-regulation of miR-29b promoted adipogenesis by enhancing SP1-mediated inhibition of TNF-α.
[83]
https://pubmed.ncbi.nlm.nih.gov/39490590/
[84]
MicroRNA Dysregulation in Parkinson's Disease: A Narrative Review
MiR-29c protects against inflammation and apoptosis in Parkinson's disease model in vivo and in vitro by targeting SP1. Clin. Exp. Pharmacol. Physiol. 47 ...
[85]
IRF5 is elevated in childhood-onset SLE and regulated by histone ...
Jul 18, 2017 · In the present study, we demonstrated that levels of mRNA expression of IRF5, IFN-α, and Sp1 were significantly increased in childhood-onset SLE ...<|separator|>