Affinage

PCSK4

Proprotein convertase subtilisin/kexin type 4 · UniProt Q6UW60

Length
755 aa
Mass
82.8 kDa
Annotated
2026-04-29
100 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PCSK4 is a germ cell-specific subtilisin/kexin-type serine proprotein convertase that functions in sperm maturation, capacitation control, and fertilization competence. It is expressed in pachytene spermatocytes and round spermatids, localizes to the sperm acrosome, and cleaves substrates including the PACAP precursor, pro-IGF-I, and pro-IGF-II at basic amino acid motifs with an optimum at pH 7.0 and 2 mM Ca²⁺ (PMID:1448111, PMID:10493908, PMID:16371590). PCSK4-null male mice are severely subfertile, exhibiting accelerated capacitation with hyper-tyrosine phosphorylation, precocious acrosome reaction, impaired zona pellucida binding, defective processing of ACRBP/sp32 and proacrosin, and embryo developmental failure (PMID:9192653, PMID:16371590, PMID:19342015, PMID:22357636). Zymogen activation requires germ cell-specific factors and involves ER retention with the chaperone GRP78/BiP, while enzyme activity is negatively regulated by the epididymal serpin CRES (PMID:21080038, PMID:22827436).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1992 High

    Identification of PCSK4 as a new proprotein convertase family member with germ cell-restricted expression established the existence of a testis-specific endoprotease likely dedicated to reproductive function.

    Evidence Northern blot, in situ hybridization, and testicular cell fractionation in rat and mouse

    PMID:1448111

    Open questions at the time
    • Enzymatic activity and substrate specificity were unknown
    • Protein localization within the spermatid was not determined
    • Function in fertilization was hypothetical
  2. 1997 High

    Genetic ablation of Pcsk4 demonstrated that it is essential for male fertility and early embryonic viability, transforming PCSK4 from a candidate gene to a functionally validated fertility factor.

    Evidence Homologous recombination knockout in mice with in vivo breeding and in vitro fertilization assays

    PMID:9192653

    Open questions at the time
    • The cellular mechanism of fertilization failure was undefined
    • Whether the embryonic defect was paternal or oocyte-derived was unclear
    • Sperm morphology appeared normal, leaving the functional defect uncharacterized
  3. 1998 High

    Reconstitution of PACAP precursor processing by PCSK4 co-expression identified the first physiological substrate, linking PCSK4 to neuropeptide maturation in the testis.

    Evidence Co-transfection in GH4C1 cells with HPLC, radioimmunoassay, and cAMP bioactivity readouts

    PMID:9493858

    Open questions at the time
    • In vivo relevance of PACAP processing by PCSK4 was not tested in knockout animals
    • Whether PACAP processing alone explains the fertility phenotype was unknown
  4. 1999 High

    Biochemical characterization of purified recombinant PCSK4 defined its catalytic properties (pH 7.0, Ca²⁺-dependent, KXXR↓ preference) and substrate range including pro-IGF-I and pro-IGF-II, distinguishing it from furin and PC1.

    Evidence Vaccinia virus expression, fluorogenic substrate kinetics, synthetic peptide and pro-peptide cleavage assays, inhibitor profiling

    PMID:10493908

    Open questions at the time
    • Substrate cleavage was demonstrated on synthetic and recombinant substrates, not in a physiological germ cell context
    • Structural basis for substrate selectivity was not determined
  5. 2005 High

    Subcellular localization to the acrosome and functional assays in null sperm revealed that PCSK4 restrains capacitation rate and is required for normal zona pellucida binding, explaining the mechanism of subfertility.

    Evidence Immunoelectron microscopy, immunofluorescence, capacitation and acrosome reaction assays, zona binding assays comparing null vs. wild-type sperm

    PMID:16371590

    Open questions at the time
    • The molecular targets through which PCSK4 regulates capacitation signaling were not identified
    • Whether accelerated capacitation is the direct cause or a correlate of reduced zona binding was unclear
  6. 2008 High

    Independent confirmation of pro-IGF-2 cleavage by highly purified PCSK4 and identification of prodomain-based and chloromethyl ketone inhibitors provided tools and validated IGF-2 maturation as a bona fide PCSK4 function.

    Evidence Leishmania expression system, purified enzyme, pro-IGF-2 cleavage assay, inhibitor kinetics

    PMID:18485734

    Open questions at the time
    • In vivo IGF-2 processing defects in PCSK4-null tissues were not assessed
    • Whether IGF-2 maturation contributes to the fertility phenotype was untested
  7. 2009 Medium

    Discovery that PCSK4-null sperm exhibit hyper-tyrosine phosphorylation and accelerated ADAM2 processing during capacitation identified specific signaling and proteolytic cascades normally held in check by PCSK4.

    Evidence Western blot time-course of capacitation in null vs. wild-type sperm with PKA inhibitors and calcium chelation

    PMID:19342015

    Open questions at the time
    • Whether PCSK4 directly cleaves ADAM2 or acts upstream was not resolved
    • Single-lab observation without independent replication
    • Identity of the PCSK4-sensitive step in the PKA/tyrosine phosphorylation cascade was not mapped
  8. 2010 Medium

    The finding that proPCSK4 is retained in the ER and interacts with GRP78/BiP in somatic cells, but not efficiently self-activated, established that germ cell-specific cofactors are required for zymogen maturation.

    Evidence Transfection in HEK293 cells, co-immunoprecipitation with GRP78/BiP, Western blot of intracellular forms

    PMID:21080038

    Open questions at the time
    • The identity of germ cell-specific activation factor(s) was not determined
    • Co-IP was performed in one direction without reciprocal validation
    • No structural insight into how the propeptide blocks activation
  9. 2012 Medium

    Proteomic and biochemical analysis of PCSK4-null sperm identified ACRBP/sp32 and proacrosin as downstream processing targets, connecting PCSK4 to the acrosin activation cascade critical for zona penetration, while the serpin CRES was identified as an endogenous inhibitor of PCSK4 activity.

    Evidence 2D-DIGE proteomics and Western blot of null vs. WT sperm (ACRBP/proacrosin); fluorogenic substrate inhibition kinetics and pro-IGF-2 cleavage assay with recombinant CRES monomer/dimer

    PMID:22357636 PMID:22827436

    Open questions at the time
    • Direct cleavage of ACRBP by PCSK4 was not reconstituted in vitro
    • CRES inhibition was shown only in vitro; in vivo relevance in epididymal sperm is inferred
    • Whether CRES regulation is the primary physiological brake on PCSK4 during sperm storage is untested
  10. 2018 Medium

    Correlative analysis of human solitary fibrous tumors showed that low PCSK4 expression coincides with accumulation of unprocessed 'big IGF-2', providing in vivo human evidence that PCSK4 is the endogenous pro-IGF-2 convertase.

    Evidence Immunohistochemistry and Western blot of tumor tissue; serum big IGF-2 measurement

    PMID:29897468

    Open questions at the time
    • Correlative human tissue study; causality not demonstrated by PCSK4 overexpression or rescue
    • Whether other convertases compensate in non-tumor tissues is unknown
    • No genetic evidence linking PCSK4 mutations to IGF-2-dependent disease in humans

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of germ cell-specific factors required for PCSK4 zymogen activation, the full repertoire of physiological substrates in the acrosome, and whether PCSK4 directly or indirectly regulates capacitation-associated signaling remain unresolved.
  • No structural model of PCSK4 exists
  • Direct cleavage of ACRBP and ADAM2 has not been reconstituted
  • No human genetic studies have linked PCSK4 mutations to male infertility

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5
Localization
GO:0005783 endoplasmic reticulum 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1474165 Reproduction 3
Partners
ACRBPADAM2CRESGRP78

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 PCSK4 (PC4) is a member of the Kex2/subtilisin-like proprotein convertase family, expressed as at least three splice variants (PC4-A, -B, -C) in testicular germ cells (pachytene spermatocytes and round spermatids) but not in Leydig, Sertoli, or peritubular cells, and its expression onset coincides with the first stages of spermiogenesis (postnatal days 19–22), indicating a reproductive developmental function. Northern analysis, testicular cell separation, in situ hybridization histochemistry, cDNA cloning Molecular endocrinology (Baltimore, Md.) High 1448111
1997 Homozygous disruption of the Pcsk4 locus in mice severely impairs male in vivo and in vitro fertility; spermatogenesis appears morphologically normal, but spermatozoa have reduced fertilizing ability and eggs fertilized by Pcsk4-null sperm fail to develop to the blastocyst stage, establishing PCSK4 as essential for fertilization and early embryonic development. Homologous recombination knockout in embryonic stem cells, breeding intercrosses, in vitro fertilization assays Proceedings of the National Academy of Sciences of the United States of America High 9192653
1998 PCSK4 processes the PACAP (pituitary adenylate cyclase-activating polypeptide) precursor into bioactive PACAP38 and PACAP27 in a co-transfection cell assay, demonstrating PACAP precursor as a physiological substrate and suggesting PCSK4 regulates PACAP-mediated germ cell maturation in the testis. Stable co-transfection of PACAP cDNA with PC4 cDNA in GH4C1 cells, reversed-phase HPLC fractionation, radioimmunoassay, Western blot, cAMP bioactivity assay Peptides High 9493858
1999 Recombinant PCSK4A (rPC4A) is an enzymatically active serine protease with optimal activity at pH 7.0 and 2 mM Ca²⁺, preferring the substrate Ac-Arg-Lys-Lys-Arg-MCA (KXXR↓ motif); it efficiently cleaves IGF-I and IGF-II pro-peptides and the PACAP precursor, with substrate specificity distinct from furin and PC1. Activity is inhibited by metal chelators, p-chloromercuribenzoic acid, transition-metal ions, and peptide semicarbazone inhibitors. Vaccinia virus recombinant expression in GH4C1 cells, fluorogenic peptide substrate kinetics (Vmax/Km), synthetic peptide cleavage assays, Western blot, inhibitor profiling The Biochemical journal High 10493908
2001 In addition to spermatids, PCSK4 is expressed in macrophage-like cells of the ovary (theca-interstitium and degenerating corpora lutea); PCSK4-null macrophage-like ovarian cells show elevated TNFα transcripts, and activation of RAW264.7 macrophages with LPS decreases PCSK4 expression while increasing TNFα, suggesting PCSK4 inversely regulates macrophage activation. β-galactosidase histoenzymatic assay (knockin reporter), RT-PCR, immunohistochemistry with macrophage markers (CD11b, F4/80), LPS activation of RAW264.7 cells Journal of reproductive immunology Medium 11164898
2005 PCSK4 localizes to acrosomal granules of round spermatids, acrosomal ridges of elongated spermatids, and the plasma membrane overlying the acrosome. PCSK4-null sperm undergo accelerated capacitation, acrosome react at lower zona pellucida concentrations, and exhibit only half the egg-binding ability of wild-type sperm, linking PCSK4's acrosomal localization to its roles in capacitation and zona binding. Immunohistochemistry, indirect immunofluorescence, immunoelectron microscopy, in vitro capacitation and acrosome reaction assays, zona pellucida egg-binding assays using PCSK4-null vs. wild-type sperm Biology of reproduction High 16371590
2008 Recombinant PCSK4 purified from a Leishmania tarentolae expression system cleaves pro-IGF-2 to produce active IGF-2, confirming a role in IGF-2 maturation. The enzyme is inhibited by the prodomain peptide rPC4(101–116) (IC₅₀ in low µM) and by tetrapeptide chloromethyl ketones (Dec-RVKR/K-cmk, Ki in low nM range). Leishmania expression and protein purification, fluorogenic substrate assays, proIGF-2 cleavage assay, inhibitor kinetics Protein expression and purification High 18485734
2009 PCSK4-null sperm show hyper-tyrosine phosphorylation during capacitation (dependent on PKA, albumin, and calcium) and increased proteolytic processing of ADAM2 from a 46-kDa to a 27-kDa form (dependent on cholesterol efflux), indicating that PCSK4 normally restrains both capacitation-associated signal transduction and ADAM2 processing. Comparative capacitation time-course experiments with wild-type vs. PCSK4-null sperm, Western blot for tyrosine phosphorylation and ADAM2 processing, PKA inhibitor and calcium chelation experiments Fertility and sterility Medium 19342015
2010 The proPCSK4 zymogen cannot efficiently self-activate in somatic (HEK293) cells and is retained in the endoplasmic reticulum, where it interacts with the molecular chaperone GRP78/BiP, suggesting that germ cell-specific factors are required for proper PCSK4 zymogen processing and activation. Transfection of rat or human PCSK4 in HEK293 cells, co-immunoprecipitation with GRP78/BiP, Western blot analysis of intracellular vs. secreted forms Molecular and cellular biochemistry Medium 21080038
2012 In PCSK4-null spermatozoa, the acrosin-binding protein ACRBP/sp32 is not proteolytically processed from its 58.5 kDa precursor to the mature 27.5 kDa form, identifying ACRBP as a candidate PCSK4 substrate (possibly indirect). Proacrosin also fails to autoactivate in PCSK4-null sperm, and morphological defects in sperm head/acrosome are detected. 2D-DIGE proteomics of PCSK4-null vs. wild-type spermatozoa, Western blot for ACRBP and proacrosin processing, immunolocalization of ACRBP Molecular human reproduction Medium 22357636
2012 The epididymal serpin CRES inhibits PCSK4 protease activity in vitro in a state-dependent manner: the CRES dimer inhibits with Ki ~8 µM, while the monomer has Ki >100 µM. Both forms block PCSK4-mediated cleavage of pro-IGF-2 in trophoblast cells, suggesting CRES is an endogenous regulator of PCSK4 activity during sperm storage. Fluorogenic substrate (Boc-RVRR-MCA) inhibition kinetics with recombinant CRES monomer and dimer, pro-IGF-2 processing assay in placental trophoblast cells Current molecular medicine Medium 22827436
2018 In solitary fibrous tumors causing non-islet cell tumor hypoglycemia (NICTH), an imbalance of high IGF2 expression relative to low PCSK4 expression is associated with accumulation of unprocessed 'big IGF2', directly implicating PCSK4 as the endogenous protease responsible for pro-IGF2 maturation in vivo. Immunohistochemistry and Western blot quantification of IGF2 and PCSK4 in tumor specimens; serum big IGF2 measurement by western immunoblotting The Journal of clinical endocrinology and metabolism Medium 29897468

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Purification, cloning, and characterization of a human coactivator, PC4, that mediates transcriptional activation of class II genes. Cell 337 8062391
1992 Testicular expression of PC4 in the rat: molecular diversity of a novel germ cell-specific Kex2/subtilisin-like proprotein convertase. Molecular endocrinology (Baltimore, Md.) 187 1448111
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
2009 Enhanced photodynamic efficacy towards melanoma cells by encapsulation of Pc4 in silica nanoparticles. Toxicology and applied pharmacology 115 19695274
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
1996 Yeast SUB1 is a suppressor of TFIIB mutations and has homology to the human co-activator PC4. The EMBO journal 101 8617240
1995 The coactivator p15 (PC4) initiates transcriptional activation during TFIIA-TFIID-promoter complex formation. The EMBO journal 100 7628453
1998 Involvement of nitric oxide during phthalocyanine (Pc4) photodynamic therapy-mediated apoptosis. Cancer research 87 9581812
1998 DNA topoisomerase I and PC4 can interact with human TFIIIC to promote both accurate termination and transcription reinitiation by RNA polymerase III. Molecular cell 79 9660958
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
2004 The single-strand DNA binding activity of human PC4 prevents mutagenesis and killing by oxidative DNA damage. Molecular and cellular biology 73 15199162
1997 C-terminal domain of transcription cofactor PC4 reveals dimeric ssDNA binding site. Nature structural biology 72 9360603
2015 Cooperation between SMYD3 and PC4 drives a distinct transcriptional program in cancer cells. Nucleic acids research 69 26350217
1994 Phosphorylation negatively regulates the function of coactivator PC4. Proceedings of the National Academy of Sciences of the United States of America 69 7809103
1998 Interaction of PC4 with melted DNA inhibits transcription. The EMBO journal 64 9724646
2010 PC4/Tis7/IFRD1 stimulates skeletal muscle regeneration and is involved in myoblast differentiation as a regulator of MyoD and NF-kappaB. The Journal of biological chemistry 59 21127072
2005 Functional characterization of core promoter elements: DPE-specific transcription requires the protein kinase CK2 and the PC4 coactivator. Molecular cell 59 15893730
2010 Sub1/PC4 a chromatin associated protein with multiple functions in transcription. RNA biology 56 20305379
1999 Coactivator PC4 mediates AP-2 transcriptional activity and suppresses ras-induced transformation dependent on AP-2 transcriptional interference. Molecular and cellular biology 56 9858613
2008 Recruitment of RNA polymerase II cofactor PC4 to DNA damage sites. The Journal of cell biology 54 19047459
2007 Activation of p53 function by human transcriptional coactivator PC4: role of protein-protein interaction, DNA bending, and posttranslational modifications. Molecular and cellular biology 50 17785449
2004 General transcriptional coactivator PC4 activates p53 function. Molecular and cellular biology 50 14966284
1998 High-affinity DNA binding by the C-terminal domain of the transcriptional coactivator PC4 requires simultaneous interaction with two opposing unpaired strands and results in helix destabilization. Journal of molecular biology 49 9512709
2001 p300-mediated acetylation of human transcriptional coactivator PC4 is inhibited by phosphorylation. The Journal of biological chemistry 47 11279157
1998 TAFII-independent activation mediated by human TBP in the presence of the positive cofactor PC4. The EMBO journal 46 9687514
2017 Yeast Sub1 and human PC4 are G-quadruplex binding proteins that suppress genome instability at co-transcriptionally formed G4 DNA. Nucleic acids research 45 28369605
1999 The adeno-associated virus type 2 regulatory proteins rep78 and rep68 interact with the transcriptional coactivator PC4. Journal of virology 45 9847329
2005 Sperm from mice genetically deficient for the PCSK4 proteinase exhibit accelerated capacitation, precocious acrosome reaction, reduced binding to egg zona pellucida, and impaired fertilizing ability. Biology of reproduction 44 16371590
2015 PC4 promotes genome stability and DNA repair through binding of ssDNA at DNA damage sites. Oncogene 41 25961912
2009 Interaction between the transactivation domain of p53 and PC4 exemplifies acidic activation domains as single-stranded DNA mimics. The Journal of biological chemistry 40 19525231
2015 Yeast transcription co-activator Sub1 and its human homolog PC4 preferentially bind to G-quadruplex DNA. Chemical communications (Cambridge, England) 39 25813861
1994 Synthesis, degradation, and subcellular localization of proteins encoded by the primary response genes TIS7/PC4 and TIS21/PC3. Journal of cellular physiology 39 8263025
1998 Properties of PC4 and an RNA polymerase II complex in directing activated and basal transcription in vitro. The Journal of biological chemistry 37 9575207
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
2004 Transcriptional coactivator PC4 stimulates promoter escape and facilitates transcriptional synergy by GAL4-VP16. Molecular and cellular biology 35 15226451
2012 Alteration in the processing of the ACRBP/sp32 protein and sperm head/acrosome malformations in proprotein convertase 4 (PCSK4) null mice. Molecular human reproduction 33 22357636
1998 Differential expression of osteopontin, PC4, and CEC5, a novel mRNA species, during in vitro angiogenesis. Experimental cell research 33 9511718
2017 Sub1/PC4, a multifaceted factor: from transcription to genome stability. Current genetics 31 28567479
2005 PC4 coactivates MyoD by relieving the histone deacetylase 4-mediated inhibition of myocyte enhancer factor 2C. Molecular and cellular biology 31 15743821
1999 Enzymic characterization in vitro of recombinant proprotein convertase PC4. The Biochemical journal 31 10493908
1998 Testis-specific prohormone convertase PC4 processes the precursor of pituitary adenylate cyclase-activating polypeptide (PACAP). Peptides 31 9493858
2012 The Rice stripe virus pc4 functions in movement and foliar necrosis expression in Nicotiana benthamiana. Virology 30 22305130
2009 Pc4, a putative movement protein of Rice stripe virus, interacts with a type I DnaJ protein and a small Hsp of rice. Virus genes 30 19130198
1998 Cloning of the human interferon-related developmental regulator (IFRD1) gene coding for the PC4 protein, a member of a novel family of developmentally regulated genes. Genomics 30 9722946
1995 Inhibition of differentiation in myoblasts deprived of the interferon-related protein PC4. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 30 7756174
1997 Primary targets for photoinactivation of vesicular stomatitis virus by AIPcS4 or Pc4 and red light. Photochemistry and photobiology 28 9077133
2006 Gradual phosphorylation regulates PC4 coactivator function. The FEBS journal 27 16689930
1995 Chromosomal assignment of the genes for proprotein convertases PC4, PC5, and PACE 4 in mouse and human. Genomics 27 7782070
2014 Mass spectrometric proteomics reveals that nuclear protein positive cofactor PC4 selectively binds to cross-linked DNA by a trans-platinum anticancer complex. Journal of the American Chemical Society 25 24524683
1999 Identification of the single-stranded DNA binding surface of the transcriptional coactivator PC4 by NMR. The Journal of biological chemistry 25 9920920
1998 Regulation of PC4/TIS7 expression in adapting remnant intestine after resection. The American journal of physiology 25 9724262
2020 Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4. Cell reports 24 33357426
1997 The human homolog of the rodent immediate early response genes, PC4 and TIS7, resides in the lung cancer tumor suppressor gene region on chromosome 3p21. Human genetics 24 9050919
1994 Nerve growth factor regulates the subcellular localization of the nerve growth factor-inducible protein PC4 in PC12 cells. Journal of neuroscience research 22 8028043
2000 Functional interaction between the HIV transactivator Tat and the transcriptional coactivator PC4 in T cells. The Journal of biological chemistry 21 10887206
2006 The intrinsically unstructured domain of PC4 modulates the activity of the structured core through inter- and intramolecular interactions. Biochemistry 20 16605275
2000 Human PC4 is a substrate-specific inhibitor of RNA polymerase II phosphorylation. The Journal of biological chemistry 20 10692395
2008 Recombinant proprotein convertase 4 (PC4) from Leishmania tarentolae expression system: purification, biochemical study and inhibitor design. Protein expression and purification 19 18485734
2007 p53 regulates its own activator: transcriptional co-activator PC4, a new p53-responsive gene. The Biochemical journal 19 17555406
2003 Growth factor regulation of PC4/TIS7, an immediate early gene expressed during gut adaptation after resection. JPEN. Journal of parenteral and enteral nutrition 19 12665168
2019 β-Fructofuranosidase and β -D-Fructosyltransferase from New Aspergillus carbonarius PC-4 Strain Isolated from Canned Peach Syrup: Effect of Carbon and Nitrogen Sources on Enzyme Production. TheScientificWorldJournal 18 30728756
2003 Alleviation of PC4-mediated transcriptional repression by the ERCC3 helicase activity of general transcription factor TFIIH. The Journal of biological chemistry 18 12590132
2016 Transcriptional Coactivator and Chromatin Protein PC4 Is Involved in Hippocampal Neurogenesis and Spatial Memory Extinction. The Journal of biological chemistry 17 27471272
2015 Substitution of tryptophan 89 with tyrosine switches the DNA binding mode of PC4. Scientific reports 17 25739870
2003 Functional characterization of the interacting domains of the positive coactivator PC4 with the transcription factor AP-2alpha. Gene 17 14597399
1996 Expression of the PC4 gene in the developing rat nervous system. Brain research 16 8919308
2016 Multifunctional human transcriptional coactivator protein PC4 is a substrate of Aurora kinases and activates the Aurora enzymes. The FEBS journal 15 26777301
2014 Transcription cofactor PC4 plays essential roles in collaboration with the small subunit of general transcription factor TFIIE. Genes to cells : devoted to molecular & cellular mechanisms 15 25308091
2020 PC4 serves as a negative regulator of skin wound healing in mice. Burns & trauma 14 32373645
2019 Nonhistone human chromatin protein PC4 is critical for genomic integrity and negatively regulates autophagy. The FEBS journal 14 31169983
2013 Bacteriophage T5 encodes a homolog of the eukaryotic transcription coactivator PC4 implicated in recombination-dependent DNA replication. Journal of molecular biology 14 24029071
2007 Characterization of the PC4 binding domain and its interactions with HNF4alpha. Journal of biochemistry 14 17317687
2023 PC4-mediated Ku complex PARylation facilitates NHEJ-dependent DNA damage repair. The Journal of biological chemistry 13 37437887
2022 Phosphorylation-dependent association of human chromatin protein PC4 to linker histone H1 regulates genome organization and transcription. Nucleic acids research 13 35670677
2020 Interaction of ASOs with PC4 Is Highly Influenced by the Cellular Environment and ASO Chemistry. Journal of the American Chemical Society 13 32374993
2018 Imbalanced Expression of IGF2 and PCSK4 Is Associated With Overproduction of Big IGF2 in SFT With NICTH: A Pilot Study. The Journal of clinical endocrinology and metabolism 13 29897468
2015 PC4 induces lymphangiogenesis dependent VEGF-C/VEGF-D/VEGFR-3 axis activation in lung adenocarcinoma. American journal of cancer research 13 26269750
2010 Coactivator function of positive cofactor 4 (PC4) in Sp1-directed luteinizing hormone receptor (LHR) gene transcription. The Journal of biological chemistry 12 21193408
1999 Inhibition of various steps in the replication cycle of vesicular stomatitis virus contributes to its photoinactivation by AlPcS4 or Pc4 and red light. Photochemistry and photobiology 12 10089828
2021 Acceleration of ageing via disturbing mTOR-regulated proteostasis by a new ageing-associated gene PC4. Aging cell 10 33957702
2016 Positive Cofactor 4 (PC4) is critical for DNA repair pathway re-routing in DT40 cells. Scientific reports 10 27374870
2014 Ceramide synthase inhibitor fumonisin B1 inhibits apoptotic cell death in SCC17B human head and neck squamous carcinoma cells after Pc4 photosensitization. Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology 10 25266739
2021 Evaluation of henipavirus chemical inactivation methods for the safe removal of samples from the high-containment PC4 laboratory. Journal of virological methods 9 34530012
2020 The large family of PC4-like domains - similar folds and functions throughout all kingdoms of life. RNA biology 9 32476604
2009 PCSK4-null sperm display enhanced protein tyrosine phosphorylation and ADAM2 proteolytic processing during in vitro capacitation. Fertility and sterility 9 19342015
2021 Genome-Wide Association Study Reveals PC4 as the Candidate Gene for Thermal Tolerance in Bay Scallop (Argopecten irradians irradians). Frontiers in genetics 8 34349776
2018 Inhibition of PC4 radiosensitizes non-small cell lung cancer by transcriptionally suppressing XLF. Cancer medicine 8 29522271
2015 Structural analysis and knock-out of a Burkholderia pseudomallei homolog of the eukaryotic transcription coactivator PC4. Gene 8 26625975
1995 Amyloid precursor protein is not processed by furin, PACE 4, PC1/3, PC2, PC4 and PC5/6 of the furin family of proprotein processing enzymes. Biochimica et biophysica acta 8 7819286
2020 Muscle overexpression of Klf15 via an AAV8-Spc5-12 construct does not provide benefits in spinal muscular atrophy mice. Gene therapy 7 32313099
2019 Multifunctional transcriptional coactivator PC4 is a global co-regulator of p53-dependent stress response and gene regulation. Journal of biochemistry 7 31236588
2018 The effect of phosphate ion on the ssDNA binding mode of MoSub1, a Sub1/PC4 homolog from rice blast fungus. Proteins 5 30561148
2014 A transmembrane domain determines the localization of rice stripe virus pc4 to plasmodesmata and is essential for its function as a movement protein. Virus research 5 24560843
2012 In vitro regulatory effect of epididymal serpin CRES on protease activity of proprotein convertase PC4/PCSK4. Current molecular medicine 5 22827436
2010 The precursor to the germ cell-specific PCSK4 proteinase is inefficiently activated in transfected somatic cells: evidence of interaction with the BiP chaperone. Molecular and cellular biochemistry 5 21080038
2025 The single-stranded DNA-binding factor SUB1/PC4 alleviates replication stress at telomeres and is a vulnerability of ALT cancer cells. Proceedings of the National Academy of Sciences of the United States of America 4 39772744
2024 Human PC4 supports telomere stability and viability in cells utilizing the alternative lengthening of telomeres mechanism. EMBO reports 4 39468351