Affinage

SUB1

Activated RNA polymerase II transcriptional coactivator p15 · UniProt P53999

Length
127 aa
Mass
14.4 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SUB1 (PC4) is a multifunctional DNA-binding transcriptional coactivator that operates at multiple stages of the RNA polymerase II transcription cycle and participates in DNA damage repair. It binds both single-stranded and double-stranded DNA through its C-terminal domain, associates with preinitiation complexes near the transcription bubble via interaction with TFIIB and the Rpb4/7 stalk, facilitates activator-dependent PIC assembly and promoter escape, modulates CTD phosphorylation through interactions with Fcp1 phosphatase and substrate-specific inhibition of CDK-mediated CTD phosphorylation, and promotes elongation by influencing Spt5 function (PMID:8617240, PMID:22055186, PMID:27924005, PMID:22973055, PMID:10692395). Its coactivator and DNA-binding activities are regulated by casein kinase II-mediated phosphorylation of the N-terminal domain, which inhibits dsDNA binding, activator interaction, and CTD kinase inhibition (PMID:7628453, PMID:16689930). Beyond transcription, SUB1/PC4 condenses chromatin through selective interaction with histones H3 and H2B, links transcription to 3′ end processing via the CPF subunit Pta1, is recruited to DNA damage sites through its ssDNA-binding activity to facilitate NHEJ, cooperates with IKAROS and IRF4 in B-cell differentiation, and drives CK2-dependent IRF1 activation in macrophage inflammatory responses (PMID:16982701, PMID:12704082, PMID:19038270, PMID:33357426, PMID:34378353).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1995 High

    Establishing PC4 as a DNA-binding transcriptional coactivator regulated by phosphorylation answered how activator-dependent transcription is facilitated beyond the general transcription factors, showing that a small dsDNA-binding protein cooperates with activators at the TFIIA-TFIID-promoter step and that CKII phosphorylation switches off this activity.

    Evidence In vitro transcription reconstitution with deletion mutants and phosphorylation assays using human PC4

    PMID:7628453

    Open questions at the time
    • Structural basis of dsDNA vs ssDNA binding not resolved
    • In vivo relevance of CKII-mediated regulation not demonstrated
  2. 1996 High

    Identification of yeast SUB1 as a TFIIB suppressor established an evolutionarily conserved functional link between the coactivator and the core initiation machinery, revealing that SUB1/PC4 modulates TFIIB-promoter interactions.

    Evidence Genetic suppressor screen of TFIIB mutations combined with in vitro TFIIB binding and in vivo transcription assays in yeast

    PMID:8617240 PMID:8702984

    Open questions at the time
    • Whether SUB1 acts through TFIIB stabilization or destabilization at different promoters was unresolved
    • Mechanism of phosphorylation-dependent regulation of TFIIB interaction unclear
  3. 1998 High

    Demonstrating that PC4 represses transcription by binding melted promoter DNA and that TFIIH relieves this repression resolved the paradox of PC4 acting as both coactivator and repressor, establishing a model where ssDNA binding at the bubble mediates repression while activator-dependent function requires TAFs and TFIIH.

    Evidence In vitro transcription with melted DNA substrates, defined minimal vs complete PIC systems, and PC4 mutant analysis

    PMID:9482861 PMID:9724646

    Open questions at the time
    • How PC4 transitions from repressive ssDNA binding to coactivation in vivo was unknown
    • Contribution of individual TAFs unresolved
  4. 1999 High

    Allele-specific genetic interactions among TFIIB, Ssu72, and Sub1 established that these three factors cooperate in transcription start site selection, placing Sub1 in a functional module controlling initiation fidelity.

    Evidence Genetic epistasis with error-prone PCR mutagenesis in yeast

    PMID:10511545

    Open questions at the time
    • Physical contacts among the three proteins at the start site were not mapped
    • Whether the mechanism involves competition for the same DNA site was unknown
  5. 2000 High

    Discovery that PC4 acts as a substrate-specific competitive inhibitor of CDK-mediated RNAPII CTD phosphorylation — and that CKII phosphorylation abolishes this activity — revealed a phosphorylation-dependent switch controlling the transition from initiation to elongation.

    Evidence In vitro kinase assays with CDK-1/-2/-7, substrate specificity analysis, and in vivo repression assays with wild-type vs mutant PC4

    PMID:10692395

    Open questions at the time
    • Which CTD phosphorylation sites are preferentially inhibited was not determined
    • In vivo kinetics of PC4 phosphorylation during the transcription cycle not established
  6. 2003 High

    Physical interaction of Sub1 with the CPF subunit Pta1 — mutually exclusive with Ssu72 binding — linked the transcription initiation factor Sub1 to 3′ end processing, providing the first evidence that Sub1 bridges the RNAPII cycle from promoter to termination.

    Evidence Genetic suppression of pta1 mutant, co-immunoprecipitation, and in vitro cleavage assays in yeast

    PMID:12704082

    Open questions at the time
    • Whether Sub1 travels with RNAPII or is recruited independently at the 3′ end unknown
    • Functional consequence for poly(A) site selection not tested
  7. 2004 High

    Showing that PC4 stimulates promoter escape (not just PIC assembly) and directly activates p53 transactivation and p53-dependent apoptosis expanded its role beyond initiation and identified a specific biological pathway (p53-bax) where PC4 coactivation is physiologically relevant.

    Evidence Quantitative in vitro transcription (promoter escape), co-immunoprecipitation with p53, reporter and apoptosis assays

    PMID:14966284 PMID:15226451

    Open questions at the time
    • Whether PC4-p53 interaction is relevant in all p53-responsive genes or gene-specific was unknown
    • Structural basis of p53 C-terminal interaction with PC4 not resolved
  8. 2005 High

    ChIP analysis showing Sub1 and Rna15 are present along gene bodies, and that sub1Δ reduces Fcp1 recruitment and alters CTD phosphorylation, established Sub1 as an elongation factor that modulates CTD phosphorylation dynamics during transcription.

    Evidence ChIP across multiple gene loci, Western blot of CTD phosphoforms, and genetic interaction analysis in yeast

    PMID:15692559

    Open questions at the time
    • Direct mechanism by which Sub1 promotes Fcp1 recruitment not established
    • Whether Sub1 effect on elongation is direct or mediated entirely through CTD phosphorylation unknown
  9. 2006 High

    Discovering that PC4 is a chromatin component that condenses chromatin through selective interaction with histones H3 and H2B, and that its depletion causes decompaction and G2/M arrest, established a structural role for PC4 beyond transcription factor interactions.

    Evidence MNase accessibility, CD spectroscopy, AFM, histone co-IP, and RNAi knockdown with cell cycle analysis in HeLa cells

    PMID:16982701

    Open questions at the time
    • Whether chromatin condensation and transcription coactivation functions are separable at specific loci was untested
    • Post-translational modifications of histones preferred by PC4 binding not mapped
  10. 2006 High

    NMR-based structural analysis of progressive N-terminal phosphorylation revealed a graded regulatory switch: sequential serine phosphorylation differentially modulates ssDNA binding, dsDNA binding, VP16 interaction, and DNA-unwinding activities, providing a structural mechanism for how CKII tunes PC4 functions.

    Evidence NMR, mass spectrometry, and biochemical binding assays with incrementally phosphorylated PC4

    PMID:16605275 PMID:16689930

    Open questions at the time
    • In vivo phosphorylation stoichiometry and dynamics not determined
    • Whether graded phosphorylation occurs at different transcription cycle stages unknown
  11. 2008 High

    Recruitment of PC4 to DNA damage sites via its ssDNA-binding capacity and stimulation of NHEJ established a direct role for PC4 in DNA double-strand break repair, independent of its transcription functions.

    Evidence Live-cell imaging with FRAP after laser microirradiation, in vitro NHEJ reconstitution, and in vivo DSB repair assays

    PMID:19038270 PMID:19047459

    Open questions at the time
    • Whether PC4 cooperates with specific NHEJ factors (Ku70/80, DNA-PKcs) was not shown
    • Relative contribution of PC4 to NHEJ vs other repair pathways not quantified
  12. 2011 High

    Quantitative proteomics placing Sub1 in the PIC near the transcription bubble, and demonstrating competition with RPA for nontemplate strand binding, unified the paradoxical repression/activation activities by showing Sub1 occupies the ssDNA binding site during initiation and is displaced as the bubble opens.

    Evidence Quantitative proteomics (MS), in vitro bubble localization, ChIP-seq, and RPA occupancy analysis in sub1Δ yeast

    PMID:22055186

    Open questions at the time
    • Time-resolved dynamics of Sub1-to-RPA handoff during initiation not captured
    • Whether this competition occurs at all promoters or is gene-specific was unknown
  13. 2012 High

    Genetic and biochemical interaction of Sub1 with the elongation factor Spt5 and kinase Bur1 revealed that Sub1 influences early elongation through modulation of Spt5 phosphorylation, connecting its initiation-proximal role to the elongation checkpoint.

    Evidence Genetic interaction analysis, co-purification, ChIP, and CTD phosphorylation biochemistry in yeast

    PMID:22973055

    Open questions at the time
    • Direct physical interaction surface between Sub1 and Spt5 not mapped
    • Whether Sub1 affects Spt5-mediated pausing in metazoans unknown
  14. 2015 High

    Crystal structure of a PC4 orthologue-DNA complex defined the molecular basis of ssDNA recognition, showing that W89 surface hydrophobicity determines the DNA binding mode, providing the first atomic-resolution view of the PC4-DNA interface.

    Evidence X-ray crystallography of MoSub1-DNA complex with W89Y mutagenesis and DNA binding analysis

    PMID:25739870

    Open questions at the time
    • Full-length PC4-DNA structure including the N-terminal domain not determined
    • How dsDNA vs ssDNA binding selectivity is achieved structurally remains incomplete
  15. 2016 High

    Identification of SUB1 as an oncogenic transcriptional activator of PLK1, C-MYC, and BUB1B in prostate cancer, regulated by miR-101, extended PC4's role to tumor biology and demonstrated direct promoter occupancy at cell cycle and proliferation genes.

    Evidence ChIP, siRNA, miRNA target validation, proliferation/invasion assays, and xenograft mouse model

    PMID:27270442

    Open questions at the time
    • Whether SUB1 oncogenic function depends on its coactivator or chromatin-condensation activity not distinguished
    • Mechanism of SUB1-mediated CDKN1B downregulation not elucidated
  16. 2017 High

    Demonstrating that Sub1 physically interacts with the Rpb4/7 stalk and Fcp1 phosphatase and that these interactions require an intact CTD revealed the structural basis for Sub1's influence on CTD phosphorylation, start site selection, and elongation rate.

    Evidence Co-immunoprecipitation, ChIP, genetic interactions, and domain mapping in yeast

    PMID:27924005

    Open questions at the time
    • Whether the Sub1-Rpb4/7 interaction is direct or bridged by another factor not resolved by crystallography
    • How the stalk-Sub1-Fcp1 module coordinates with TFIIB interactions is unknown
  17. 2020 High

    Purification of a PC4-IKAROS-IRF4 complex from B cells and demonstration that PC4 deficiency reduces IKAROS protein and impairs antibody production established PC4 as a tissue-specific chromatin organizer in adaptive immunity.

    Evidence Complex purification/MS, B-cell-specific conditional knockout mice, gene expression and antibody production analysis

    PMID:33357426

    Open questions at the time
    • How PC4 stabilizes IKAROS protein mechanistically is unclear
    • Whether the PC4-IKAROS-IRF4 module operates in other immune cell lineages is untested
  18. 2021 High

    Myeloid-specific knockout of Sub1 reduced proatherosclerotic TLR signaling and shifted macrophage polarization from M1 to M2, with CK2-dependent Irf1 activation identified as the downstream mechanism, establishing SUB1 as a master regulon of innate immune inflammatory transcription.

    Evidence Myeloid-specific conditional knockout in ApoE−/− mice, bone marrow transplant, promoter analysis, and Irf1 rescue experiments

    PMID:34378353

    Open questions at the time
    • Whether this pathway operates in human macrophages not confirmed
    • Direct physical interaction between Sub1 and CK2 at the Irf1 promoter not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how PC4 transitions between its distinct chromatin-condensation, transcription coactivation, and DNA repair functions at specific genomic loci; whether the graded phosphorylation switch operates dynamically during a single transcription cycle in vivo; and how the PC4-IKAROS and PC4-IRF1 modules integrate with its general transcription factor activities.
  • No time-resolved in vivo analysis of PC4 phosphorylation dynamics during transcription
  • No genome-wide separation of chromatin condensation vs coactivation targets
  • Structural basis of full-length PC4 in complex with RNAPII not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 7 GO:0098772 molecular function regulator activity 2 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 1
Pathway
R-HSA-74160 Gene expression (Transcription) 13 R-HSA-73894 DNA Repair 4 R-HSA-168256 Immune System 1 R-HSA-4839726 Chromatin organization 1 R-HSA-5357801 Programmed Cell Death 1 R-HSA-8953854 Metabolism of RNA 1
Partners
FCP1IKZF1IRF4RPB4RPB7SPT5TFIIBTP53
Complex memberships
RNA polymerase II preinitiation complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Yeast SUB1 was isolated as a suppressor of TFIIB mutations; SUB1 binds to TFIIB in vitro and inhibits formation of TBP-TFIIB-promoter complexes, and overexpression of SUB1 stimulates transcriptional activation in vivo. The N-terminal third of SUB1 is highly similar to mammalian coactivator PC4. Genetic suppressor screen, in vitro binding assay, in vivo transcription assay The EMBO journal High 8617240
1996 Yeast TSP1 (SUB1 homolog) stimulates basal RNA polymerase II transcription, binds both single- and double-stranded DNA, interacts with a general transcription factor and a transcriptional activator, and phosphorylation appears to regulate these interactions. In vitro transcription assay, DNA binding assay, protein interaction assay, phosphorylation analysis The Journal of biological chemistry High 8702984
1995 Human PC4 (SUB1 ortholog) binds both double-stranded and single-stranded DNA; dsDNA binding correlates with coactivator function; phosphorylation by casein kinase II inhibits dsDNA binding and coactivator activity; PC4 cooperates with activator GAL4-AH during TFIIA-TFIID-promoter complex formation. In vitro transcription assay, DNA binding assay, deletion mutagenesis, phosphorylation assay The EMBO journal High 7628453
1998 Human PC4 coactivator function requires TAFs (in TFIID) and TFIIH; PC4 strongly represses transcription initiation by minimal preinitiation complexes lacking TAFs and TFIIH while promoting their assembly; TFIIH and TAFII250 can both phosphorylate PC4. In vitro transcription assay, preinitiation complex assembly assay, kinase assay Proceedings of the National Academy of Sciences of the United States of America High 9482861
1998 PC4 represses transcription by interacting with melted (unpaired) DNA through its C-terminal domain; this inhibitory activity is attenuated by TFIIH and by phosphorylation of PC4; interaction with melted promoters is not required for activator-dependent transcription. In vitro transcription assay, DNA binding assay with melted DNA substrates, mutant PC4 analysis The EMBO journal High 9724646
1999 Genetic analysis revealed allele-specific interactions among TFIIB, Ssu72, and Sub1 in yeast; sub1Δ and ssu72-1 mutations are allele-specific enhancers of tfiib mutations that affect transcription start site selection, demonstrating functional interactions among TFIIB, Ssu72, and Sub1 in the mechanism of start site selection. Genetic epistasis, error-prone PCR mutagenesis screen, allele-specific interaction analysis Genetics High 10511545
2003 Sub1 interacts physically with Pta1 (a subunit of the cleavage/polyadenylation factor CPF), and overexpression of SUB1 suppresses the growth and processing defect of a pta1 mutation; physical interactions of Ssu72 and Sub1 with Pta1 are mutually exclusive; Sub1 interacts with both Pta1 of CPF and TFIIB, linking transcription and 3′ end processing machineries. Genetic suppression, biochemical interaction (co-IP/pulldown), in vitro cleavage assay Genes & development High 12704082
2004 Human PC4 enhances DNA binding of p53 to its cognate site in vitro and directly interacts with p53 in vivo; the C-terminal 30 amino acids of p53 strongly interact with PC4; PC4 stimulates p53-mediated transactivation and p53-dependent apoptosis by inducing bax gene expression. In vitro DNA binding assay, co-immunoprecipitation, transactivation reporter assay, apoptosis assay Molecular and cellular biology High 14966284
2004 PC4 stimulates promoter escape in GAL4-VP16-dependent transcription (in addition to PIC assembly); this effect requires TFIIA and TAF subunits of TFIID; PC4 physically interacts with TFIIH and GAL4-VP16 through its coactivator domain, and these interactions are regulated by PC4 phosphorylation. In vitro transcription assay (quantitative), physical interaction assay, phosphorylation analysis Molecular and cellular biology High 15226451
2005 Sub1 and Rna15 (yeast CstF-64 homolog) are recruited to promoters and present along the length of yeast genes; cells lacking Sub1 show decreased Fcp1 (RNAPII phosphatase) accumulation, altered RNAPII CTD phosphorylation, and decreased crosslinking of RNAPII to transcribed genes, indicating Sub1 facilitates elongation by influencing CTD-modifying enzymes. ChIP, genetic interaction analysis (allele-specific), Western blot of CTD phosphorylation forms The EMBO journal High 15692559
2006 Human PC4 is a bona fide chromatin component; it selectively interacts with core histones H3 and H2B; this interaction mediates chromatin condensation as demonstrated by MNase accessibility, circular dichroism, and AFM; PC4 knockdown in HeLa cells causes chromatin decompaction and upregulates genes leading to G2/M checkpoint arrest. MNase accessibility assay, CD spectroscopy, AFM, co-immunoprecipitation with histones, RNAi knockdown, cell cycle analysis Molecular and cellular biology High 16982701
2006 Phosphorylation of PC4's N-terminal unstructured domain (up to 8 serines, progressively) differentially regulates its activities: one phosphoserine slightly enhances ssDNA binding; ≥2 phosphoserines decrease DNA-unwinding activity and abrogate VP16 binding; phosphorylation gradually decreases dsDNA binding affinity. NMR, mass spectrometry, biochemical binding assays The FEBS journal High 16689930
2006 The PC4 C-terminal domain (PC4ctd) is sufficient for ssDNA, dsDNA, and VP16 activation domain binding; VP16 and DNA binding are mutually exclusive; the unstructured N-terminal domain (PC4ntd) increases VP16 interaction but decreases ssDNA binding and DNA-unwinding activity without affecting dsDNA binding. NMR titration, biochemical binding assays, docking experiments Biochemistry High 16605275
2008 PC4 accumulates at DNA damage sites induced by chemical agents or laser microirradiation; this recruitment is independent of poly(ADP-ribosyl)ation and γH2AX but depends on its single-strand DNA binding capacity; PC4 shows high turnover at damage sites, suggesting a role in early DNA damage response. Live cell microscopy, FRAP, laser microirradiation, fluorescent fusion protein mutant analysis The Journal of cell biology High 19047459
2008 PC4 stimulates ligase-mediated DNA end joining and nonhomologous end-joining (NHEJ) of noncomplementary DNA ends in vitro; PC4 helps in association of DNA ends through its C-terminal domain; PC4 activates DSB repair activity in vivo. In vitro DNA end joining assay, pulldown, cell-free NHEJ extract assay, in vivo DSB repair assay Journal of molecular biology High 19038270
2000 Human PC4 acts as a substrate-specific inhibitor of RNA polymerase II CTD phosphorylation: it competitively inhibits cdk-1, -2, and -7-mediated phosphorylation of the RNAPII largest subunit but not other substrates of the same kinases; phosphorylated PC4 lacks this kinase inhibitory activity; wild-type but not kinase-inhibitory-deficient PC4 represses transcription in vivo. In vitro kinase assay, competitive inhibition analysis, in vivo transcription repression assay with mutant PC4 The Journal of biological chemistry High 10692395
2000 PC4 interacts with the HIV Tat transactivator in vitro and in vivo (co-immunoprecipitation); PC4 overexpression enhances Tat-dependent activation of the HIV LTR; the basic transactivation-responsive binding domain of Tat is required for PC4 interaction; PC4 residues 22-91 (lysine-rich domain) are required; casein kinase II phosphorylation of PC4 inhibits Tat interaction. Yeast two-hybrid, in vitro binding, co-immunoprecipitation, transient transfection reporter assay, domain mapping The Journal of biological chemistry High 10887206
2011 Sub1 (yeast PC4 homolog) is a component of RNA polymerase II preinitiation complexes (PICs) identified by quantitative proteomics; Sub1 localizes near the transcription bubble in vitro; Sub1 binds to promoters in vivo dependent upon PIC assembly; deletion or ssDNA-binding mutation of Sub1 leads to increased RPA levels at active promoters, suggesting competition for a common ssDNA binding site on the nontemplate strand during initiation. Quantitative proteomics (MS), in vitro transcription bubble localization, ChIP-seq, genetic analysis Molecular cell High 22055186
2012 Sub1 genetically interacts with SPT5 (elongation factor); Sub1 influences Spt5 phosphorylation of the RNAPII CTD by kinase Bur1; Sub1 and Spt5 copurify in the same complex during early transcription elongation; Sub1 influences Spt5-Rpb1 interaction and transcription elongation rate of constitutive and inducible genes. Genetic interaction analysis, co-purification, ChIP, biochemical analysis of CTD phosphorylation Molecular biology of the cell High 22973055
2008 Sub1 represses IMD2 gene expression in yeast; sub1Δ increases IMD2 expression and confers resistance to mycophenolate; Sub1 localizes around the IMD2 promoter region and requires the upstream region of the transcription start site for repression, revealing a transcription repressor function of Sub1. Genetic interaction analysis, gene expression assay, ChIP Genes to cells Medium 18823333
2015 SMYD3 histone methyltransferase interacts with human PC4; PC4 depletion results in loss of SMYD3-mediated H3K4me3 and target gene expression; SMYD3 and PC4 localize at target genes in a mutually dependent manner; PC4 contributes to SMYD3 transactivation by stabilizing SMYD3 occupancy at target genes. Co-immunoprecipitation, ChIP, gene expression analysis, siRNA knockdown, artificial tethering Nucleic acids research High 26350217
2016 miR-101 targets SUB1/PC4 and negatively regulates its expression in prostate cancer; SUB1 knockdown reduces cell proliferation, invasion, and migration in vitro and tumor growth and metastasis in vivo; ChIP shows SUB1 binds promoters of PLK1, C-MYC, and BUB1B oncogenes and activates their expression; SUB1 also downregulates CDKN1B. miRNA target validation, siRNA knockdown, ChIP, in vitro proliferation/invasion/migration assays, xenograft mouse model Oncogene High 27270442
2017 Sub1 physically interacts with the RNAPII stalk domain (Rpb4/7 heterodimer), likely through its C-terminal region, and associates with Fcp1 phosphatase; a complete CTD is necessary for proper Sub1 association to chromatin and RNAPII; Sub1-Rpb4/7-Fcp1 interaction modulates CTD phosphorylation, transcription start site selection, and elongation rate, likely by influencing the clamp function. Co-immunoprecipitation, ChIP, genetic interaction analysis, domain mapping Nucleic acids research High 27924005
2007 PC4 is a p53-inducible gene; p53 binds to multiple sites in the PC4 promoter in vitro and in vivo; p53 acts as transcriptional activator of PC4; both PC4 mRNA and protein increase in response to p53-inducing stimuli; PC4 enhances p53 recruitment to the PC4 promoter, establishing a positive feedback loop. Reporter assay, ChIP, EMSA, RT-PCR, Western blot The Biochemical journal Medium 17555406
2013 Yeast Sub1 is required for NHEJ repair of DSBs in plasmid DNA but not in chromosomal DNA, revealing that these two repair contexts are not equivalent and that Sub1/PC4 has a context-specific role in NHEJ. Plasmid NHEJ assay, chromosomal DSB repair assay (HO endonuclease), yeast deletion mutant PloS one Medium 23554872
2015 Sub1 protects DNA from oxidative damage in vivo and in vitro; SUB1 mRNA is induced by oxidative stress; sub1Δ mutant has increased chromosomal DNA strand breaks after peroxide treatment; purified Sub1 protein directly protects DNA from metal ion-catalyzed oxidative damage. In vitro DNA protection assay, comet assay, mRNA induction assay, yeast deletion mutant Molecular and cellular biochemistry Medium 26708217
2015 Crystal structure of PC4 orthologue MoSub1 in complex with DNA revealed that residue Y74 (equivalent to W89 in PC4) interacts with a single nucleotide; W89 in wild-type PC4 interacts with two nucleotides; surface hydrophobicity around residue 89 determines the DNA binding mode of PC4. X-ray crystallography, mutagenesis (W89Y), DNA binding analysis Scientific reports High 25739870
2020 PC4 orchestrates chromatin structure and gene expression in mature B cells; the PC4 complex purified from B cells contains transcription factors IKAROS and IRF4; PC4 deficiency reduces IKAROS protein levels, causing de-repression of target genes; IRF4 reciprocally induces PC4 expression via a super-enhancer; PC4-deficient B cells show impaired antibody production. Complex purification/MS, B-cell-specific conditional knockout mice, antibody production assay, gene expression analysis Cell reports High 33357426
2021 Sub1/PC4 is identified as a master regulon of macrophage TLR2/TLR4 response; myeloid-specific Sub1 knockout in ApoE-/- mice reduces proatherosclerotic TLR effects; Sub1-knockout macrophages show enhanced M2 polarization and cholesterol efflux; promoter analysis reveals Sub1-dependent activation of Irf1 transcription in a CK2-dependent manner; Irf1 overexpression in Sub1-KO macrophages restores M1 skewing. Transgenic myeloid-specific knockout, bone marrow transplant, promoter analysis, macrophage polarization assays Advanced science High 34378353
2022 PC4 (encoded by SUB1) acts as a DNA lesion sensor; downregulation of PC4 by pyridostatin dramatically promotes cytotoxicity of trans-PtTz toward HeLa cells by retarding repair of 1,3-trans-PtTz crosslinked DNA lesions mediated by PC4. MS proteomics, siRNA knockdown, cytotoxicity assay, DNA repair assay Nucleic acids research Medium 35258624

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 666 18185590
2000 Smad2, Smad3 and Smad4 cooperate with Sp1 to induce p15(Ink4B) transcription in response to TGF-beta. The EMBO journal 344 11013220
2008 The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15(Ink4b). Nature structural & molecular biology 247 18836456
1997 Frequent hypermethylation of p16 and p15 genes in multiple myeloma. Blood 181 9116295
2008 Development of submergence-tolerant rice cultivars: the Sub1 locus and beyond. Annals of botany 173 18974101
2006 p14-MP1-MEK1 signaling regulates endosomal traffic and cellular proliferation during tissue homeostasis. The Journal of cell biology 172 17178906
1995 Deletion of the p16 and p15 genes in human bladder tumors. Journal of the National Cancer Institute 172 7563186
1995 Codeletion of p15 and p16 in primary malignant mesothelioma. Oncogene 137 7630635
1997 Impaired fertility in mice deficient for the testicular germ-cell protease PC4. Proceedings of the National Academy of Sciences of the United States of America 127 9192653
2003 Functional interactions between the transcription and mRNA 3' end processing machineries mediated by Ssu72 and Sub1. Genes & development 125 12704082
1996 Frequent codeletion of p16/MTS1 and p15/MTS2 and genetic alterations in p16/MTS1 in pancreatic tumors. Gastroenterology 120 8613012
1998 A dynamic model for PC4 coactivator function in RNA polymerase II transcription. Proceedings of the National Academy of Sciences of the United States of America 109 9482861
1989 Ionomycin-regulated phosphorylation of the myeloid calcium-binding protein p14. Nature 105 2478889
1996 Yeast SUB1 is a suppressor of TFIIB mutations and has homology to the human co-activator PC4. The EMBO journal 101 8617240
2002 A major predisposition locus for severe obesity, at 4p15-p14. American journal of human genetics 100 11957135
2001 SUB1, an Arabidopsis Ca2+-binding protein involved in cryptochrome and phytochrome coaction. Science (New York, N.Y.) 100 11161203
2000 Adenovirus-mediated p14(ARF) gene transfer in human mesothelioma cells. Journal of the National Cancer Institute 100 10772681
1995 The coactivator p15 (PC4) initiates transcriptional activation during TFIIA-TFIID-promoter complex formation. The EMBO journal 100 7628453
2001 p15(PAF), a novel PCNA associated factor with increased expression in tumor tissues. Oncogene 99 11313979
2002 Adenovirus-mediated overexpression of p14(ARF) induces p53 and Bax-independent apoptosis. Oncogene 92 12082630
1998 Involvement of the Ink4 proteins p16 and p15 in T-lymphocyte senescence. Oncogene 92 9704925
1996 Alterations of the p15, p16,and p18 genes in osteosarcoma. Cancer genetics and cytogenetics 92 8603340
1998 Involvement of nitric oxide during phthalocyanine (Pc4) photodynamic therapy-mediated apoptosis. Cancer research 87 9581812
2012 Hypermethylation-mediated silencing of p14(ARF) in fibroblasts from idiopathic pulmonary fibrosis. American journal of physiology. Lung cellular and molecular physiology 82 22707614
2000 Alterations and hypermethylation of the p14(ARF) gene in gastric cancer. International journal of cancer 82 10925358
1999 Alteration of p16 and p15 genes in human uterine tumours. British journal of cancer 82 10408854
2011 Sub1 and RPA associate with RNA polymerase II at different stages of transcription. Molecular cell 80 22055186
2006 Transcriptional coactivator PC4, a chromatin-associated protein, induces chromatin condensation. Molecular and cellular biology 78 16982701
1996 A yeast transcriptional stimulatory protein similar to human PC4. The Journal of biological chemistry 77 8702984
2005 The transcriptional coactivator PC4/Sub1 has multiple functions in RNA polymerase II transcription. The EMBO journal 76 15692559
2002 Frequent abnormalities of the p15 and p16 genes in mycosis fungoides and sezary syndrome. The Journal of investigative dermatology 76 11874489
2018 LncRNA SNHG17 promotes gastric cancer progression by epigenetically silencing of p15 and p57. Journal of cellular physiology 75 30256413
1999 Mutational analysis of yeast TFIIB. A functional relationship between Ssu72 and Sub1/Tsp1 defined by allele-specific interactions with TFIIB. Genetics 75 10511545
2015 Cooperation between SMYD3 and PC4 drives a distinct transcriptional program in cancer cells. Nucleic acids research 69 26350217
1998 Interaction of PC4 with melted DNA inhibits transcription. The EMBO journal 64 9724646
2008 High frequency of hypermethylation of p14, p15 and p16 in oral pre-cancerous lesions associated with betel-quid chewing in Sri Lanka. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 59 18284544
2016 MicroRNA-101 regulated transcriptional modulator SUB1 plays a role in prostate cancer. Oncogene 57 27270442
2010 Sub1/PC4 a chromatin associated protein with multiple functions in transcription. RNA biology 56 20305379
2008 Bmi1 promotes prostate tumorigenesis via inhibiting p16(INK4A) and p14(ARF) expression. Biochimica et biophysica acta 54 18817867
2008 The p14 FAST protein of reptilian reovirus increases vesicular stomatitis virus neuropathogenesis. Journal of virology 54 18971262
2008 Recruitment of RNA polymerase II cofactor PC4 to DNA damage sites. The Journal of cell biology 54 19047459
2007 FOXO transcription factor-dependent p15(INK4b) and p19(INK4d) expression. Oncogene 54 17873901
1997 Alteration of p16 and p15 genes in common epithelial ovarian tumors. International journal of cancer 51 9133447
2004 General transcriptional coactivator PC4 activates p53 function. Molecular and cellular biology 50 14966284
1996 Alterations of retinoblastoma, p53, p16(CDKN2), and p15 genes in human astrocytomas. Cancer 46 8674005
2015 Interplay between promoter methylation and chromosomal loss in gene silencing at 3p11-p14 in cervical cancer. Epigenetics 43 26291246
2001 Alterations of INK4a(p16-p14ARF)/INK4b(p15) expression and telomerase activation in meningioma progression. Journal of neuro-oncology 42 11859969
1999 Functional evidence for a role of combined CDKN2A (p16-p14(ARF))/CDKN2B (p15) gene inactivation in malignant gliomas. Acta neuropathologica 41 10541865
2015 Core clock, SUB1, and ABAR genes mediate flooding and drought responses via alternative splicing in soybean. Journal of experimental botany 38 26314767
2008 Human transcriptional coactivator PC4 stimulates DNA end joining and activates DSB repair activity. Journal of molecular biology 36 19038270
2001 The testicular germ-cell protease PC4 is also expressed in macrophage-like cells of the ovary. Journal of reproductive immunology 36 11164898
2006 Influence of methylated p15 and p16 genes on clinicopathological features in colorectal cancer. Journal of gastroenterology and hepatology 35 16872319
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