Affinage

SP1

DAN domain family member 5 · UniProt Q8N907

Length
189 aa
Mass
20.2 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SP1 is a sequence-specific transcription factor that activates RNA polymerase II transcription through GC-box DNA elements bound by its C-terminal Zn(II) fingers, with separate domains controlling DNA-binding affinity and transactivation (PMID:3059495). It assembles into stacked tetramers at DNA loop junctures, enabling long-range transcriptional synergism between distal and proximal GC boxes (PMID:2062845), and cooperates combinatorially with partner factors at adjacent sites — STAT1 for interferon-gamma-dependent ICAM-1 activation (PMID:8530443), Oct1 for U2 snRNA gene activation (PMID:19070619), and the retinoblastoma protein, which potentiates SP1 transactivation in part by liberating it from a negative regulator (PMID:1588949, PMID:8007947, PMID:9591776). SP1 activity is countered at GC boxes by the competing repressor Sp3 (PMID:8070411) and by nuclear hormone receptors ERα/ERβ that bind its C-terminus to redirect transcription at GC-rich promoters (PMID:10681512). SP1 function is heavily tuned by a layered post-translational code: phosphorylation by PKA, ERK2, cyclin A-CDK, CDK1, JNK1, and ATM modulates its DNA binding, stability, and chromatin residence (PMID:9261118, PMID:9918860, PMID:11598016, PMID:19245816, PMID:25398907, PMID:34550526); O-GlcNAcylation blocks specific cofactor interactions (PMID:19070619); and a SUMO/ubiquitin axis governs turnover, in which SUMO modification at Lys16 recruits the E3 ligase RNF4 for proteasomal degradation while phosphorylation events (e.g. JNK1/CDK1 at Thr739) or counteracting deubiquitinases (USP39, ZRANB1) protect the protein (PMID:21983342, PMID:24706897, PMID:34197957, PMID:34765294). Through these inputs SP1 integrates cell-cycle, stress, and signaling cues: ATM-driven SUMO/RNF4 degradation enforces senescence (PMID:34550526), CDK1/Pin1-controlled phosphorylation displaces SP1 from chromosomes during mitosis to permit cell-cycle progression (PMID:25398907), and caspase cleavage at Asp183 yields a pro-apoptotic fragment (PMID:29236199). SP1 also directs developmental and differentiation programs — maintaining the epithelial state via miR-200 (PMID:24627491), hematopoietic differentiation robustness (PMID:31164147), primordial follicle formation through Notch2 (PMID:31282930), and a TRRAP-dependent neuronal microtubule program (PMID:33594975) — and is recruited by chromatin regulators including SIRT6, which binds its zinc-finger domain to repress mTOR-pathway genes (PMID:31372634), and HDAC2 (PMID:37205635).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 1988 High

    Established the modular architecture of SP1, separating DNA recognition from transactivation and defining it as a bona fide Pol II activator.

    Evidence Deletion mutagenesis with E. coli-expressed fragments in an in vitro transcription assay

    PMID:3059495

    Open questions at the time
    • Did not define the structural basis of GC-box recognition
    • Activation domain cofactor partners not identified
  2. 1991 High

    Answered how SP1 mediates synergy between distant promoter elements by showing it tetramerizes and loops DNA.

    Evidence Conventional and scanning transmission EM of SP1-DNA complexes

    PMID:2062845

    Open questions at the time
    • Multimerization interface not mapped at residue level
    • In vivo relevance of looping geometry not tested
  3. 1994 High

    Defined how SP1 output is set at shared GC boxes by the competing repressor Sp3 and by Rb-mediated relief of an inhibitor.

    Evidence Competition/chimera reporter assays in SL2 cells; EMSA, recombinant Rb addition, and biochemical fractionation identifying Sp1-I

    PMID:8007947 PMID:8070411

    Open questions at the time
    • Molecular identity of the ~20 kDa Sp1-I inhibitor not fully resolved
    • Direct vs. indirect Rb effect on SP1 DNA binding
  4. 1995 High

    Demonstrated combinatorial transcriptional synergy by showing SP1 physically partners with STAT1 at contiguous sites for interferon-gamma-dependent gene activation.

    Evidence Reciprocal co-IP from primary cells, EMSA, and reporter assays at the ICAM-1 promoter

    PMID:8530443

    Open questions at the time
    • Interaction surface not mapped
    • Generality across other STAT-SP1 target genes not established
  5. 1997 Medium

    Showed phosphorylation can directly enhance SP1, linking PKA signaling to SP1 DNA-binding and transcriptional activity.

    Evidence In vitro kinase assay with recombinant SP1 plus PKA agonist/antagonist reporter pharmacology

    PMID:9261118

    Open questions at the time
    • Phosphoacceptor residues not mapped
    • In vivo PKA target sites not confirmed
  6. 1999 Medium

    Placed SP1 downstream of the Ras-ERK cascade, with ERK2 phosphorylation stimulating SP1 DNA binding for growth-factor-inducible transcription.

    Evidence In vitro ERK2 phosphorylation, EMSA, dephosphorylation, and MEK-inhibitor epistasis at the gastrin promoter

    PMID:9918860

    Open questions at the time
    • Specific ERK2 sites on SP1 not identified
    • Single-promoter context
  7. 2000 High

    Explained how estrogen signaling routes through SP1, with ERα/ERβ binding the SP1 C-terminus and using AF-1 to activate GC-rich promoters.

    Evidence Co-IP, pull-down, chimeric ER mapping, and AF-1 deletion reporter assays

    PMID:10681512

    Open questions at the time
    • SP1 residues contacted by ER not mapped
    • Endogenous target gene repertoire not defined
  8. 2001 High

    Connected SP1 to cell-cycle control by showing cyclin A-CDK binds and phosphorylates SP1 at an N-terminal site to augment its DNA binding and activity.

    Evidence Co-IP, in vitro/in vivo phosphorylation, binding-site selection, and phospho-site mutagenesis reporter assays

    PMID:11598016

    Open questions at the time
    • Exact target gene programs in S phase not delineated
  9. 2002 Medium

    Showed inflammatory signaling downregulates SP1, with LPS-driven Ser/Thr dephosphorylation and degradation reducing SP1-dependent gene expression.

    Evidence EMSA, IP-Western, in vitro dephosphorylation, and RT-PCR in a mouse lung model

    PMID:12089157

    Open questions at the time
    • Phosphatase responsible not identified
    • Degradation pathway not defined
  10. 2008 Medium

    Integrated phosphorylation, sumoylation and ubiquitination into a coordinated processing/degradation program controlling SP1 turnover.

    Evidence In vitro SUMO/ubiquitination assays, site-directed mutagenesis, pulse-chase, and kinase inhibitor studies

    PMID:18239466

    Open questions at the time
    • E3 ligase not identified at this stage
    • Protease for N-terminal cleavage unknown
  11. 2008 Medium

    Demonstrated SP1 is required for HDAC-inhibitor-induced TRAIL expression and apoptosis, linking SP1 to death-ligand transcription.

    Evidence Reporter constructs, ChIP, SP1 knockdown, and SP1-knockout mouse ES cells with apoptosis assays

    PMID:18701496

    Open questions at the time
    • Direct SP1 binding element on TRAIL promoter not detailed
    • Mechanism of HDAC-inhibitor-driven SP1 activation unclear
  12. 2008 Medium

    Revealed O-GlcNAcylation as a switch that blocks specific SP1 cofactor interactions, suppressing SP1-Oct1 cooperative activation.

    Evidence Co-IP, O-GlcNAc site mapping, mutagenesis, and reporter assays at the U2 snRNA gene

    PMID:19070619

    Open questions at the time
    • Whether O-GlcNAc affects other partners not tested
    • Dynamic regulation in vivo not addressed
  13. 2009 Medium

    Showed Hsp90 chaperones SP1 stability during mitosis via JNK1-mediated phosphorylation, preventing proteasomal degradation.

    Evidence Co-IP, geldanamycin treatment, shRNA knockdown, JNK1-site mutagenesis, and ubiquitination assay

    PMID:19245816

    Open questions at the time
    • E3 ligase not yet identified
    • Direct vs. JNK1-dependent Hsp90 effect not separated
  14. 2011 High

    Identified RNF4 as the SUMO-targeted E3 ligase for SP1 and showed mitotic JNK1 phosphorylation at Thr739 protects SP1 from degradation.

    Evidence In vitro/in vivo ubiquitination, co-IP, and Lys16/Thr739 mutagenesis with proteasome inhibition

    PMID:21983342

    Open questions at the time
    • Cell-cycle stoichiometry of SUMO-to-ubiquitin handoff not quantified
  15. 2014 High

    Resolved how mitotic SP1 is stabilized and removed from chromosomes by showing Pin1 binds phospho-Thr739 to drive CDK1 multisite phosphorylation.

    Evidence X-ray crystallography of Pin1-pThr739 peptide, ITC, in vitro phosphorylation, ChIP, and cell-cycle analysis

    PMID:25398907

    Open questions at the time
    • Genes regulated by chromosome-displaced SP1 during mitosis not enumerated
  16. 2014 High

    Dissected opposing SUMO paralog effects, showing SUMO2 at Lys683/Lys16 attenuates DNA binding and increases turnover while SUMO1 is positive, controlling differentiation.

    Evidence In vivo/in vitro sumoylation, site mutagenesis, EMSA, ChIP, and a Lgr5-KI reporter mouse

    PMID:24706897

    Open questions at the time
    • SUMO ligases directing paralog choice not fully defined
  17. 2014 Medium

    Established PML nuclear bodies as a sequestration mechanism that SUMOylates SP1 and removes it from target promoters.

    Evidence ChIP, IF co-localization, nuclear matrix co-fractionation, sumoylation assay, and PML RING/SBM mutants

    PMID:24728382

    Open questions at the time
    • Reversibility/release from PML bodies not characterized
    • Target gene scope not defined
  18. 2014 Medium

    Defined an SP1-dependent epithelial maintenance program by showing SP1 activates the miR-200 family, antagonized by ZEB in mesenchymal states.

    Evidence ChIP, reporter assays, EMSA, SP1 knockdown, and in vivo embryonic co-expression analysis

    PMID:24627491

    Open questions at the time
    • Mechanism of ZEB-mediated block on SP1 activity not resolved
  19. 2018 High

    Showed proteolytic conversion of SP1 to a pro-apoptotic effector via caspase cleavage at Asp183 generating the apoptosis-inducing Sp1-70C fragment.

    Evidence In vitro caspase cleavage, D183A mutagenesis, and gain/loss-of-function apoptosis assays

    PMID:29236199

    Open questions at the time
    • Transcriptional targets of Sp1-70C not defined
    • Which caspase acts in vivo not pinned down
  20. 2019 High

    Identified SIRT6 as a deacetylase-independent repressor that binds the SP1 zinc-finger domain to restrain mTOR-pathway gene transcription.

    Evidence Domain-mapping co-IP, ChIP, reporter assays, mTOR-inhibitor rescue, and muscle-specific SIRT6 knockout mice

    PMID:31372634

    Open questions at the time
    • How SIRT6 binding blocks SP1 without deacetylation not mechanistically resolved
  21. 2019 Medium

    Showed SP1 chromatin binding maintains robustness of cell-fate transitions rather than dictating chromatin accessibility during hematopoiesis.

    Evidence Sp1ΔDBD knock-in ES cells with hematopoietic differentiation, ATAC-seq, ChIP-seq, and single-cell expression

    PMID:31164147

    Open questions at the time
    • Direct target genes governing fate timing not isolated
  22. 2020 Medium

    Connected SP1 to ovarian development by showing it directly drives Notch2 transcription required for primordial follicle formation.

    Evidence Cell-type-specific knockdown, ChIP at the Notch2 promoter, and renal capsule transplantation in mice

    PMID:31282930

    Open questions at the time
    • Upstream control of SP1 in pregranulosa cells not defined
  23. 2021 High

    Showed DNA-damage signaling drives SP1 destruction via ATM-Ser101 phosphorylation triggering Lys16 SUMO and RNF4 degradation to enforce senescence.

    Evidence S101A/K16R mutagenesis, ATM and proteasome inhibitors, sumoylation assay, and senescence-marker analysis

    PMID:34550526

    Open questions at the time
    • SP1 target genes whose loss drives senescence not enumerated
  24. 2021 Medium

    Identified deubiquitinases that oppose SP1 degradation, with USP39 and ZRANB1 directly binding and stabilizing SP1 to support proliferation and cancer phenotypes.

    Evidence Co-IP, ubiquitination assays, cycloheximide chase, knockdown/rescue, and xenografts

    PMID:34197957 PMID:34765294

    Open questions at the time
    • DUB site specificity on SP1 ubiquitin chains not mapped
    • Single-lab reports for each DUB
  25. 2021 Medium

    Placed SP1 in a Keap1/cullin-RING ubiquitin network, acting as both a Keap1 ubiquitination substrate and a transcriptional regulator of CUL4A.

    Evidence Co-IP, ubiquitination assays, ChIP, siRNA knockdown, and reporter assays

    PMID:33895141

    Open questions at the time
    • Direct vs. indirect Keap1-SP1 ubiquitination not fully separated
  26. 2021 High

    Demonstrated SP1 chromatin recruitment depends on TRRAP, defining a conserved SP1-driven microtubule-dynamics program in neurons.

    Evidence ChIP-seq in conditional Trrap knockout mice, multi-omics, and Stathmin3/4 rescue

    PMID:33594975

    Open questions at the time
    • Whether TRRAP acts via SP1 acetylation or recruitment not resolved
  27. 2023 Medium

    Revealed SP1-stabilizing feedforward circuits in cancer, including SIRPA-ERK-Thr278 phosphorylation/SLC7A3 arginine uptake and HDAC2-mediated SP1 acetylation controlling macrophage polarization.

    Evidence Phospho-site mutagenesis, ChIP, ERK/proteasome inhibitors, and multiple murine tumor models

    PMID:37205635 PMID:37769797

    Open questions at the time
    • Acetylation sites on SP1 modified by HDAC2 not mapped
    • Generality of the SP1 stabilization circuit beyond osteosarcoma untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dozens of competing post-translational inputs are quantitatively integrated to set context-specific SP1 target-gene selection remains unresolved.
  • No unified model linking PTM combinations to specific gene programs
  • Structural basis of cofactor selection at GC boxes incomplete
  • Genome-wide SP1 target maps across signaling states not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953897 Cellular responses to stimuli 1
Partners
ESR1PIN1PMLRB1RNF4SIRT6STAT1TRRAP
Complex memberships
PML nuclear bodies

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 Sp1 contains distinct regions for DNA binding and transcriptional activation: Zn(II) fingers confer sequence-specific DNA binding, a separate region regulates DNA-binding affinity, and at least two distinct segments contribute to transcriptional activation of RNA polymerase II in vitro. Deletion mutagenesis, E. coli expression of Sp1 fragments, in vitro transcription assay Science High 3059495
1991 Sp1 forms tetramers and assembles multiple stacked tetramers at DNA loop junctures, mediating long-range transcriptional synergism between distal and proximal GC box elements via DNA looping. Conventional and scanning transmission electron microscopy of Sp1-DNA complexes Proceedings of the National Academy of Sciences of the United States of America High 2062845
1992 Retinoblastoma protein (Rb) positively regulates Sp1 transcriptional activity; using a GAL4-Sp1 fusion protein, Rb was shown to directly stimulate Sp1-mediated transactivation in vivo. GAL4-Sp1 fusion co-transfection, reporter gene assay Molecular and cellular biology Medium 1588949
1994 Sp3 represses Sp1-mediated transcriptional activation by competing with Sp1 for common GC-box DNA binding sites; chimeric protein analysis showed that neither the glutamine-rich A/B domains nor the D domain of Sp1 can be functionally replaced by the homologous Sp3 regions. Co-transfection reporter assays in mammalian cells and Sp-factor-deficient Drosophila SL2 cells, antibody generation, chimeric protein expression The EMBO journal High 8070411
1994 Rb stimulates Sp1-mediated transactivation by liberating Sp1 from a ~20 kDa negative regulator protein (Sp1-I); recombinant Rb reversed Sp1-I-mediated inhibition of Sp1 DNA binding, and Sp1-I was identified as an RB-associated protein. Mobility shift assay, antibody supershift, recombinant protein addition, co-transfection with GAL4-Sp1, identification of Sp1-I by biochemical fractionation Molecular and cellular biology Medium 8007947
1995 Stat1 and Sp1 physically interact (co-immunoprecipitation from primary cells without overexpression) and both must occupy contiguous DNA binding sites for full interferon-gamma-dependent activation of the ICAM-1 gene, demonstrating transcriptional synergy. Co-immunoprecipitation, DNA/protein binding assay (EMSA), transfected reporter assays The Journal of biological chemistry High 8530443
1997 cAMP-dependent protein kinase (PKA) activates Sp1 transcriptional and DNA-binding activity; recombinant Sp1 DNA-binding activity is stimulated by exogenous PKA in vitro, and PKA antagonists inhibit Sp1-dependent reporter activity. In vitro kinase assay with recombinant Sp1, insect-cell co-transfection reporter assay, PKA agonist/antagonist pharmacology The Journal of biological chemistry Medium 9261118
1998 Rb physically associates with Sp1 in nuclear complexes across all cell cycle phases (reciprocal co-immunoprecipitation and supershift), and this association potentiates Sp1-mediated transcription of the DHFR promoter through its GC box. Co-immunoprecipitation, EMSA supershift, immunodepletion, co-transfection reporter assay with GC-box point mutant Oncogene High 9591776
1999 ERK2 phosphorylates Sp1 and stimulates its DNA-binding activity; pretreatment of cell extracts with recombinant ERK2 increased Sp1 binding, while dephosphorylation reduced it. The Ras-ERK cascade mediates EGF-inducible gastrin promoter activation through Sp1. In vitro phosphorylation with recombinant ERK2, EMSA, dephosphorylation assay, co-transfection with dominant-negative/active constructs, MEK inhibitor (PD98059) Biochemical and biophysical research communications Medium 9918860
2000 ERα and ERβ physically interact with Sp1 (co-immunoprecipitation) and preferentially bind the C-terminal region of Sp1 (pull-down assay); the AF-1 domain (amino acids 79–117) of ERα is required for transcriptional activation at GC-rich Sp1 promoter elements. Co-immunoprecipitation, pull-down assay, chimeric ER expression, transactivation reporter assay, AF-1 deletion analysis The Journal of biological chemistry High 10681512
2001 Cyclin A-CDK complexes physically interact with Sp1 (co-immunoprecipitation) and phosphorylate it in vitro and in vivo at an N-terminal site; this phosphorylation augments Sp1 DNA-binding activity and transcriptional activation. Mutation of the phosphorylation site abolished cyclin A-CDK-dependent effects. Co-immunoprecipitation, in vitro and in vivo phosphorylation assay, DNA binding site selection/PCR, co-transfection reporter assay, phosphorylation-site mutagenesis The EMBO journal High 11598016
2002 LPS dephosphorylates Sp1 at serine and threonine residues (but not tyrosine) in vivo and promotes Sp1 protein degradation, both of which reduce Sp1 DNA-binding activity and decrease expression of Sp1-dependent target genes (eNOS, COX-1). EMSA, immunoprecipitation-Western blot, in vitro dephosphorylation, nuclear fractionation, RT-PCR, in vivo mouse lung model The Journal of biological chemistry Medium 12089157
2007 Sp1 undergoes phosphorylation-driven proteolytic processing, desumoylation, and degradation: Ser59 regulates N-terminal cleavage; Lys16 is the SUMO-1/ubiquitin target; Ser7 enhances ubiquitination; PKCα and the PKC-ERK-ERBB2 axis drive Sp1 processing. CyclinA/CDK2 phosphorylation of Ser59 relieves SUMO-mediated repression. In vitro sumoylation/ubiquitination assays, site-directed mutagenesis, kinase inhibitor studies, pulse-chase, co-transfection Cell cycle Medium 18239466
2008 O-GlcNAc modification within the second serine/threonine-rich region of Sp1 inhibits the physical interaction between Sp1 and Oct1, thereby suppressing cooperative activation of the U2 snRNA gene. Co-immunoprecipitation, O-GlcNAc site mapping, transcriptional reporter assay, site-directed mutagenesis FEBS letters Medium 19070619
2009 Hsp90 interacts with Sp1 during mitosis and maintains Sp1 stability via JNK1-mediated phosphorylation at Thr278 and Thr739; inhibition or knockdown of Hsp90 decreases JNK1 activity and leads to ubiquitin-dependent proteasomal degradation of Sp1 during mitosis. Co-immunoprecipitation, geldanamycin treatment, shRNA knockdown, site-directed mutagenesis of JNK1 phosphorylation sites, ubiquitination assay Journal of molecular biology Medium 19245816
2011 RNF4 is the ubiquitin E3 ligase for Sp1: sumoylated Sp1 (at Lys16) recruits RNF4, leading to proteasomal degradation. JNK1-mediated phosphorylation of Sp1 at Thr739 during mitosis abolishes the Sp1-RNF4 interaction, protecting Sp1 from degradation and maintaining its levels for cell division. In vitro and in vivo ubiquitination assays, co-immunoprecipitation, site-directed mutagenesis (Lys16, Thr739), domain mapping, proteasome inhibitor Journal of molecular biology High 21983342
2014 Pin1 is recruited to the phospho-Thr739-Pro motif of Sp1 and facilitates CDK1-mediated phosphorylation at Ser720, Thr723, and Thr737 during mitosis; X-ray crystallography confirmed Pin1 binding to the pThr739 peptide. Increased CDK1 phosphorylation stabilizes Sp1 (via reduced RNF4 interaction) and displaces it from chromosomes, facilitating cell cycle progression. Isothermal titration calorimetry, X-ray crystallography, site-directed mutagenesis, co-immunoprecipitation, in vitro phosphorylation, ChIP, cell cycle analysis Nucleic acids research High 25398907
2014 SUMO2 negatively regulates Sp1 by: (1) sumoylating Sp1 at Lys683 to attenuate DNA binding; (2) sumoylating Sp1 at Lys16 to increase its turnover; and (3) interfering with the Sp1-p300 coactivator interaction and recruiting Sp3 repressor. SUMO1 positively regulates Sp1 and forms complexes with it; these differential SUMO modifications control lens cell differentiation. Co-immunoprecipitation, in vivo and in vitro sumoylation assays, site-directed mutagenesis (K683, K16), EMSA, ChIP, reporter assays, SUMO1/2/3 knockdown/overexpression, Lgr5-KI reporter mouse model Proceedings of the National Academy of Sciences of the United States of America High 24706897
2018 Caspase cleavage of Sp1 at Asp183 (identified in vitro) produces a 70 kDa C-terminal fragment (Sp1-70C, aa 184–785); the Sp1-D183A mutant is resistant to cleavage and renders cells resistant to apoptotic stimuli, whereas Sp1-70C overexpression induces apoptosis, demonstrating that caspase cleavage of Sp1 promotes apoptosis. In vitro caspase cleavage assay, site-directed mutagenesis (D183A), ectopic expression of cleavage-resistant and truncated Sp1 forms, apoptosis assays (DNA damage, TRAIL) Apoptosis High 29236199
2019 SIRT6 binds directly to the zinc finger DNA-binding domain of Sp1 and represses its transcriptional activity, independent of SIRT6 deacetylase activity; SIRT6 deficiency increases Sp1 occupancy at mTOR signaling gene promoters, activating mTOR and increasing global protein synthesis. Co-immunoprecipitation, domain-mapping pull-down, ChIP, reporter assays, mTOR inhibitor rescue, muscle-specific SIRT6 knockout mice, pharmacological inhibition Nucleic acids research High 31372634
2021 ATM phosphorylation of Sp1 (at Ser101) in response to DNA damage triggers its sumoylation at Lys16 and subsequent RNF4-mediated proteasomal degradation, driving cellular senescence; Sp1 phospho-null (S101A) or sumo-null (K16R) mutants resist degradation and reduce senescence markers. Site-directed mutagenesis (S101A, K16R), ATM inhibitor, proteasome inhibitor, sumoylation assay, senescence marker analysis (SA-β-gal, p21, p16) GeroScience High 34550526
2021 USP39 deubiquitinates and stabilizes SP1 protein, prolonging its half-life; SP1 is identified as a substrate of USP39, and knockdown of USP39 promotes SP1 degradation, with SP1 overexpression reversing USP39-knockdown-induced apoptosis and cell cycle arrest. Co-immunoprecipitation, ubiquitination assay, cycloheximide chase (half-life measurement), siRNA knockdown/rescue, in vivo xenograft Cellular signalling Medium 34197957
2021 ZRANB1 directly binds SP1 and stabilizes it through deubiquitination; ZRANB1-SP1 axis regulates LOXL2 transcription to promote HCC growth and metastasis. Co-immunoprecipitation, ubiquitination assay, gain/loss-of-function studies, RNA-seq, xenograft American journal of cancer research Medium 34765294
2021 TRRAP is required for SP1 binding at promoters of microtubule dynamics genes in Purkinje neurons; TRRAP loss reduces SP1 chromatin occupancy and disrupts a conserved SP1-dependent transcriptional program, with ectopic expression of Stathmin3/4 rescuing TRRAP-deficient neuronal defects. Integrated transcriptomics, epigenomics (ChIP-seq), proteomics, conditional Trrap knockout mice, ectopic gene expression rescue eLife High 33594975
2021 Sp1 is a substrate of Keap1: Sp1 physically interacts with Keap1, which promotes Sp1 ubiquitination. Sp1 in turn regulates CUL4A expression by binding its promoter, and SP1 regulates Nrf2 protein levels via the CRL4AWDR23 ubiquitin ligase complex. Co-immunoprecipitation, ubiquitination assay, ChIP, siRNA knockdown, reporter assays, Western blot The Journal of biological chemistry Medium 33895141
2014 Sp1 binds to the miR-200b~200a~429 proximal promoter and activates miR-200 family expression in epithelial cells, maintaining the epithelial state; in mesenchymal cells, ZEB-mediated repression blocks Sp1's ability to activate the miR-200 promoter despite maintained Sp1 expression. Knockdown of Sp1 induces EMT-associated marker changes. ChIP, reporter assay, Sp1 siRNA knockdown, EMSA, in vivo embryonic co-expression analysis The Journal of biological chemistry Medium 24627491
2023 HDAC2 regulates the M2-like TAM phenotype via acetylation of histone H3 and transcription factor SP1; pharmacologic or genetic HDAC2 inhibition reverses protumor macrophage polarization through the HDAC2-SP1 axis. HDAC2 genetic deletion (myeloid-specific KO), pharmacological HDAC inhibition, ChIP for SP1 acetylation, co-culture systems, four murine lung cancer models Cancer research Medium 37205635
2014 Sp1 binds the GSDME promoter at the -36 to -28 site and promotes GSDME gene transcription; Sp1 knockdown or inhibition suppresses GSDME expression and reduces chemotherapy-induced pyroptosis. The regulation synergizes with STAT3 activity and antagonizes DNA methylation. ChIP, luciferase reporter assay, Sp1 siRNA knockdown, Sp1 inhibitor, STAT3 inhibitor, DNA methylation analysis Cell death & disease Medium 38238307
2008 Sp1 is responsible for TRAIL induction by HDAC inhibitor MS275 alone or combined with Adriamycin in breast cancer cells; Sp1-knockout mouse embryonic stem cells and Sp1-knockdown cells are resistant to TRAIL induction and apoptosis by these combined treatments. Reporter constructs, ChIP, Sp1 siRNA knockdown, Sp1-knockout mouse embryonic stem cells, apoptosis assays Cancer research Medium 18701496
2014 Pin1 interacts with the phospho-Thr739-Pro motif of Sp1 (confirmed by ITC and X-ray crystallography of Pin1 with the pThr739 peptide occupying Pin1 active site); this interaction promotes CDK1-mediated multisite phosphorylation of Sp1 (Ser720, Thr723, Thr737) during mitosis. X-ray crystallography, isothermal titration calorimetry, in vitro phosphorylation, co-IP Nucleic acids research High 25398907
2014 PML induces SUMOylation of Sp1 in a RING-motif-dependent manner; SUMOylated Sp1 is recruited into PML nuclear bodies through interaction with PML's SUMO-binding motif, reducing Sp1 binding to target gene promoters and suppressing Sp1 transactivation. ChIP, immunofluorescence co-localization, nuclear matrix co-fractionation, SUMOylation assay, co-immunoprecipitation, PML RING and SBM mutants PloS one Medium 24728382
2020 SP1 governs primordial follicle formation in mice by controlling NOTCH2 expression: SP1 directly binds the Notch2 gene promoter in pregranulosa cells; knockdown of Sp1 in somatic cells suppresses nest breakdown, oocyte apoptosis, and primordial follicle formation. Conditional knockdown (Lgr5-KI reporter mouse, FOXL2+ cell-specific knockdown), ChIP for SP1 at Notch2 promoter, renal capsule transplantation Journal of molecular cell biology Medium 31282930
2019 SP1 is required for stable hematopoietic differentiation trajectories; Sp1 DNA-binding domain mutation (Sp1ΔDBD/ΔDBD) distorts cell fate decision timing during hematopoiesis without dramatically altering distal accessible chromatin patterns, indicating Sp1 chromatin binding maintains robustness of differentiation rather than directing chromatin accessibility. Sp1ΔDBD/ΔDBD knock-in ES cells, hematopoietic differentiation assay, ATAC-seq, ChIP-seq, single-cell gene expression analysis Epigenetics & chromatin Medium 31164147
2023 SIRPA phosphorylates SP1 at Thr278 via ERK activation, protecting SP1 from proteasomal degradation; stabilized SP1 binds the SLC7A3 promoter to increase arginine uptake, which in turn further stabilizes SP1 in an ERK-independent manner, forming a 'SP1 stabilization circle' that promotes osteosarcoma metastasis. Co-immunoprecipitation, phosphorylation site mutagenesis (T278), proteasome inhibitor, ChIP for SP1 at SLC7A3 promoter, ERK inhibitor, xenograft model Cancer letters Medium 37769797

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Sp1- and Krüppel-like transcription factors. Genome biology 833 12620113
1994 Sp1-mediated transcriptional activation is repressed by Sp3. The EMBO journal 676 8070411
1991 Developmental expression of Sp1 in the mouse. Molecular and cellular biology 528 2005904
2015 Sp1 and the 'hallmarks of cancer'. The FEBS journal 448 25393971
2004 Gene regulation by Sp1 and Sp3. Biochemistry and cell biology = Biochimie et biologie cellulaire 354 15284899
2015 Sp1 transcription factor: A long-standing target in cancer chemotherapy. Pharmacology & therapeutics 346 25960131
1988 Distinct regions of Sp1 modulate DNA binding and transcriptional activation. Science (New York, N.Y.) 336 3059495
2000 Ligand-, cell-, and estrogen receptor subtype (alpha/beta)-dependent activation at GC-rich (Sp1) promoter elements. The Journal of biological chemistry 331 10681512
2010 The role of Sp1 and Sp3 in normal and cancer cell biology. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 284 20810260
1992 The retinoblastoma gene product regulates Sp1-mediated transcription. Molecular and cellular biology 260 1588949
1995 Stat1 depends on transcriptional synergy with Sp1. The Journal of biological chemistry 238 8530443
1991 DNA looping and Sp1 multimer links: a mechanism for transcriptional synergism and enhancement. Proceedings of the National Academy of Sciences of the United States of America 238 2062845
1997 Modulation of transcription factor Sp1 by cAMP-dependent protein kinase. The Journal of biological chemistry 196 9261118
1994 The retinoblastoma gene product RB stimulates Sp1-mediated transcription by liberating Sp1 from a negative regulator. Molecular and cellular biology 189 8007947
1999 Sp1 phosphorylation by Erk 2 stimulates DNA binding. Biochemical and biophysical research communications 181 9918860
2005 The family feud: turning off Sp1 by Sp1-like KLF proteins. The Biochemical journal 168 16266294
2011 Sp1 expression regulates lung tumor progression. Oncogene 119 22158040
2022 TFRC upregulation promotes ferroptosis in CVB3 infection via nucleus recruitment of Sp1. Cell death & disease 110 35821227
2011 Targeting Sp1 transcription factors in prostate cancer therapy. Medicinal chemistry (Shariqah (United Arab Emirates)) 104 22022994
2001 Cyclin A-CDK phosphorylates Sp1 and enhances Sp1-mediated transcription. The EMBO journal 103 11598016
2001 Transactivation via RAR/RXR-Sp1 interaction: characterization of binding between Sp1 and GC box motif. Molecular endocrinology (Baltimore, Md.) 93 11579201
2006 Overexpression of Sp1 transcription factor induces apoptosis. Oncogene 91 16715126
2021 LSD1-Demethylated LINC01134 Confers Oxaliplatin Resistance Through SP1-Induced p62 Transcription in HCC. Hepatology (Baltimore, Md.) 87 34322883
2007 Sp1 and Sp3 regulate basal transcription of the survivin gene. Biochemical and biophysical research communications 79 17350596
2008 Sp1 and p73 activate PUMA following serum starvation. Carcinogenesis 73 18579560
2014 Sp1-mediated microRNA-182 expression regulates lung cancer progression. Oncotarget 72 24519909
2014 Sumoylation differentially regulates Sp1 to control cell differentiation. Proceedings of the National Academy of Sciences of the United States of America 70 24706897
2008 Regulation of Sp1 by cell cycle related proteins. Cell cycle (Georgetown, Tex.) 69 18769160
2012 Crosstalk of Sp1 and Stat3 signaling in pancreatic cancer pathogenesis. Cytokine & growth factor reviews 65 22342309
2011 Interplay of posttranslational modifications in Sp1 mediates Sp1 stability during cell cycle progression. Journal of molecular biology 63 21983342
2006 Downregulation of transcription factor, Sp1, during cellular senescence. Biochemical and biophysical research communications 63 17161377
2019 Circular RNA circSCAF11 Accelerates the Glioma Tumorigenesis through the miR-421/SP1/VEGFA Axis. Molecular therapy. Nucleic acids 62 31400609
2014 Specificity protein 1 (Sp1) maintains basal epithelial expression of the miR-200 family: implications for epithelial-mesenchymal transition. The Journal of biological chemistry 59 24627491
2015 Sp1 cooperates with Sp3 to upregulate MALAT1 expression in human hepatocellular carcinoma. Oncology reports 54 26352013
2000 Tau promoter confers neuronal specificity and binds Sp1 and AP-2. Journal of neurochemistry 54 10987820
2008 SP1 protein-based nanostructures and arrays. Nano letters 53 18193911
2005 Sp1 and Sp3 activate transcription of the human dopamine transporter gene. Journal of neurochemistry 52 15816870
2002 Lipopolysaccharide down-regulates Sp1 binding activity by promoting Sp1 protein dephosphorylation and degradation. The Journal of biological chemistry 52 12089157
1993 Comparison of DNA-binding properties between BTEB and Sp1. Journal of biochemistry 51 8276776
2023 The HDAC2-SP1 Axis Orchestrates Protumor Macrophage Polarization. Cancer research 50 37205635
2018 P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated astroglial autophagy. Cell death & disease 47 29749377
2002 Sp1 is essential for estrogen receptor alpha gene transcription. The Journal of steroid biochemistry and molecular biology 46 12429135
2003 E2F and Sp1/Sp3 Synergize but are not sufficient to activate the MYCN gene in neuroblastomas. The Journal of biological chemistry 44 14645238
2002 Sp1 and Egr1 regulate transcription of the Dmrt1 gene in Sertoli cells. Biology of reproduction 44 11870074
1998 Retinoblastoma protein associates with SP1 and activates the hamster dihydrofolate reductase promoter. Oncogene 44 9591776
2021 USP39 promotes tumorigenesis by stabilizing and deubiquitinating SP1 protein in hepatocellular carcinoma. Cellular signalling 43 34197957
2019 SIRT6 transcriptionally regulates global protein synthesis through transcription factor Sp1 independent of its deacetylase activity. Nucleic acids research 43 31372634
1990 A naturally occurring gamma globin gene mutation enhances SP1 binding activity. Molecular and cellular biology 43 1688466
2013 Sp1 and c-Myc regulate transcription of BMI1 in nasopharyngeal carcinoma. The FEBS journal 42 23601184
1996 buttonhead and D-Sp1: a novel Drosophila gene pair. Mechanisms of development 42 8892232
2008 Sp1-mediated TRAIL induction in chemosensitization. Cancer research 38 18701496
2024 Chronic Stress-Induced and Tumor Derived SP1+ Exosomes Polarizing IL-1β+ Neutrophils to Increase Lung Metastasis of Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 37 39630109
2008 Sp1 transcription factor as a target for anthracyclines: effects on gene transcription. Biochimie 37 18226599
2024 Transcription factor Sp1 transcriptionally enhances GSDME expression for pyroptosis. Cell death & disease 36 38238307
2020 SP1 governs primordial folliculogenesis by regulating pregranulosa cell development in mice. Journal of molecular cell biology 36 31282930
2008 MT-SP1 proteolysis and regulation of cell-microenvironment interactions. Frontiers in bioscience : a journal and virtual library 36 17981566
2007 Phosphorylation mediates Sp1 coupled activities of proteolytic processing, desumoylation and degradation. Cell cycle (Georgetown, Tex.) 36 18239466
2020 The SP1-12LOX axis promotes chemoresistance and metastasis of ovarian cancer. Molecular medicine (Cambridge, Mass.) 34 32375633
2008 Transcriptional regulation of BRD7 expression by Sp1 and c-Myc. BMC molecular biology 33 19111069
1999 Expression of MXI1, a Myc antagonist, is regulated by Sp1 and AP2. The Journal of biological chemistry 33 10497252
2023 SIRPA enhances osteosarcoma metastasis by stabilizing SP1 and promoting SLC7A3-mediated arginine uptake. Cancer letters 32 37769797
2022 Role of Sp1 in atherosclerosis. Molecular biology reports 32 35715606
2019 SP1 regulates KLF4 via SP1 binding motif governed by DNA methylation during odontoblastic differentiation of human dental pulp cells. Journal of cellular biochemistry 31 31009133
2009 Heat shock protein 90 is important for Sp1 stability during mitosis. Journal of molecular biology 31 19245816
2018 Caspase cleavage of transcription factor Sp1 enhances apoptosis. Apoptosis : an international journal on programmed cell death 28 29236199
2018 Sp1-regulated transcription of RasGRP1 promotes hepatocellular carcinoma (HCC) proliferation. Liver international : official journal of the International Association for the Study of the Liver 28 29655291
2017 Downregulation of decidual SP1 and P300 is associated with severe preeclampsia. Journal of molecular endocrinology 28 29273682
2008 O-GlcNAc modification of Sp1 inhibits the functional interaction between Sp1 and Oct1. FEBS letters 28 19070619
2021 Sp1-Mediated circRNA circHipk2 Regulates Myogenesis by Targeting Ribosomal Protein Rpl7. Genes 26 34066653
2020 SP1/TGF‑β1/SMAD2 pathway is involved in angiogenesis during osteogenesis. Molecular medicine reports 26 32016481
2019 Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors. Epigenetics & chromatin 26 31164147
2014 Pin1-mediated Sp1 phosphorylation by CDK1 increases Sp1 stability and decreases its DNA-binding activity during mitosis. Nucleic acids research 26 25398907
2020 ZEB1 Mediates Fibrosis in Corneal Endothelial Mesenchymal Transition Through SP1 and SP3. Investigative ophthalmology & visual science 25 32721022
2023 Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer. Journal of translational medicine 24 37147632
2019 Sp1 in Astrocyte Is Important for Neurite Outgrowth and Synaptogenesis. Molecular neurobiology 23 31317491
2018 SP1 reduces autophagic flux through activating p62 in gastric cancer cells. Molecular medicine reports 23 29328444
2018 MiR-150-3p targets SP1 and suppresses the growth of glioma cells. Bioscience reports 23 29654167
2016 The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells. Molecular endocrinology (Baltimore, Md.) 23 27182621
2002 Sp1 transactivation of the TCL1 oncogene. The Journal of biological chemistry 23 12421830
2012 Apolipoprotein E4 is deficient in inducing macrophage ABCA1 expression and stimulating the Sp1 signaling pathway. PloS one 22 22984509
2002 Sp1 and Sp3 activate the rat connexin40 proximal promoter. Biochemical and biophysical research communications 22 11890673
2020 SP1-independent inhibition of FOXM1 by modified thiazolidinediones. European journal of medicinal chemistry 21 33069434
2020 Targeting the NCOA3-SP1-TERT axis for tumor growth in hepatocellular carcinoma. Cell death & disease 21 33239622
2021 Beyond HAT Adaptor: TRRAP Liaisons with Sp1-Mediated Transcription. International journal of molecular sciences 20 34830324
2021 DNA damage-induced degradation of Sp1 promotes cellular senescence. GeroScience 19 34550526
2021 Deubiquitinase ZRANB1 drives hepatocellular carcinoma progression through SP1-LOXL2 axis. American journal of cancer research 19 34765294
2021 HAT cofactor TRRAP modulates microtubule dynamics via SP1 signaling to prevent neurodegeneration. eLife 18 33594975
2011 Gata4 and Sp1 regulate expression of the erythropoietin receptor in cardiomyocytes. Journal of cellular and molecular medicine 18 21029371
2010 Sp1 phosphorylation is involved in myelin basic protein gene transcription. Journal of neuroscience research 18 20882567
2002 Steroid hormones, endometrial gene regulation and the Sp1 family of proteins. Journal of the Society for Gynecologic Investigation 18 12445596
2024 Role of Specificity Protein 1 (SP1) in Cardiovascular Diseases: Pathological Mechanisms and Therapeutic Potentials. Biomolecules 17 39062521
2008 Butyrate-induced phosphatase regulates VEGF and angiogenesis via Sp1. Archives of biochemistry and biophysics 17 18655767
2019 SP1 and RARα regulate AGAP2 expression in cancer. Scientific reports 16 30674964
2005 Sp1 and Sp3 regulate basal transcription of the human CYP2F1 gene. Drug metabolism and disposition: the biological fate of chemicals 16 15860659
2021 Sp1 is a substrate of Keap1 and regulates the activity of CRL4AWDR23 ubiquitin ligase toward Nrf2. The Journal of biological chemistry 15 33895141
2018 SP1 upregulated FoxO3a promotes tumor progression in colorectal cancer. Oncology reports 15 29565456
2015 Down-regulation of EPHX2 gene transcription by Sp1 under high-glucose conditions. The Biochemical journal 15 26341485
2014 Inhibition of Sp1 functions by its sequestration into PML nuclear bodies. PloS one 15 24728382
2010 Sp1 and KLF15 regulate basal transcription of the human LRP5 gene. BMC genetics 15 20141633
2003 Sp1 and Sp3 Are important regulators of AP-2gamma gene transcription. Biology of reproduction 14 12801994

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