host cell factor c1


Summary: A cellular transcriptional coactivator that contains N-terminal KELCH REPEATS and N- and C-terminal FIBRONECTIN TYPE III DOMAINS. It functions as a transcription factor for a number of genes and in the assembly of IMMEDIATE-EARLY PROTEINS of the HERPES SIMPLEX VIRUS. Mutations in the HCFC1 gene are associated with cases of X-LINKED MENTAL RETARDATION.

Top Publications

  1. Wysocka J, Myers M, Laherty C, Eisenman R, Herr W. Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Genes Dev. 2003;17:896-911 pubmed
    ..These results suggest that HCF-1 can broadly regulate transcription, both positively and negatively, through selective modulation of chromatin structure. ..
  2. Wilson A, LaMarco K, Peterson M, Herr W. The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein. Cell. 1993;74:115-25 pubmed
    ..When expressed in human cells, this large open reading frame encodes both the 300 kd and smaller HCF polypeptides, indicating that the smaller polypeptides arise by processing of the 300 kd protein. ..
  3. Ruan H, Han X, Li M, Singh J, Qian K, Azarhoush S, et al. O-GlcNAc transferase/host cell factor C1 complex regulates gluconeogenesis by modulating PGC-1? stability. Cell Metab. 2012;16:226-37 pubmed publisher
    ..approach, we identified a broad variety of proteins associated with O-GlcNAc transferase (OGT), among which host cell factor C1 (HCF-1) is highly abundant...
  4. Piluso D, Bilan P, Capone J. Host cell factor-1 interacts with and antagonizes transactivation by the cell cycle regulatory factor Miz-1. J Biol Chem. 2002;277:46799-808 pubmed
  5. Wilson A, Peterson M, Herr W. The HCF repeat is an unusual proteolytic cleavage signal. Genes Dev. 1995;9:2445-58 pubmed
    ..Modulation of this noncovalent association may provide a mechanism for regulating HCF activity. For example, the cleaved products of an alternative mRNA splicing variant of HCF do not remain associated. ..
  6. Izeta A, Malcomber S, O Hare P. Primary structure and compartmentalization of Drosophila melanogaster host cell factor. Gene. 2003;305:175-83 pubmed
    ..Finally, we also show that dHCF is unable to rescue the tsBN67 cell cycle arrest phenotype. These results indicate that dHCF is an orthologue of HCF-1, although both proteins might not be functionally exchangeable. ..
  7. Wysocka J, Reilly P, Herr W. Loss of HCF-1-chromatin association precedes temperature-induced growth arrest of tsBN67 cells. Mol Cell Biol. 2001;21:3820-9 pubmed
    ..We propose that the role of HCF-1 in cell proliferation is to regulate gene transcription by associating with a multiplicity of DNA-bound transcription factors through its VP16 interaction domain. ..
  8. Nogueira M, Wang V, Tantin D, Sharp P, Kristie T. Herpes simplex virus infections are arrested in Oct-1-deficient cells. Proc Natl Acad Sci U S A. 2004;101:1473-8 pubmed
    ..The results have implications for both the HSV lytic and latency-reactivation cycles. ..
  9. Julien E, Herr W. A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1. Mol Cell. 2004;14:713-25 pubmed
    ..These results establish the HCF-1C subunit as an important M phase regulator and suggest that H4-K20 methylation status contributes to chromosome behavior during mitosis and proper cytokinesis. ..

More Information


  1. Knez J, Piluso D, Bilan P, Capone J. Host cell factor-1 and E2F4 interact via multiple determinants in each protein. Mol Cell Biochem. 2006;288:79-90 pubmed
    ..Our findings show that HCF-1 and E2F4 interact via multiple determinants and suggest a linkage between E2F4 and HCF-1 cell growth pathways. ..
  2. Tyagi S, Chabes A, Wysocka J, Herr W. E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. Mol Cell. 2007;27:107-19 pubmed
    ..These results suggest that HCF-1 induces cell-cycle-specific transcriptional activation by E2F proteins to promote cell proliferation. ..
  3. Li J, Ebata A, Dong Y, Rizki G, Iwata T, Lee S. Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator. PLoS Biol. 2008;6:e233 pubmed publisher
    ..As HCF-1 is highly conserved, our findings have important implications for aging and FOXO regulation in mammals. ..
  4. Misaghi S, Ottosen S, Izrael Tomasevic A, Arnott D, Lamkanfi M, Lee J, et al. Association of C-terminal ubiquitin hydrolase BRCA1-associated protein 1 with cell cycle regulator host cell factor 1. Mol Cell Biol. 2009;29:2181-92 pubmed publisher
  5. Kristie T, Sharp P. Purification of the cellular C1 factor required for the stable recognition of the Oct-1 homeodomain by the herpes simplex virus alpha-trans-induction factor (VP16). J Biol Chem. 1993;268:6525-34 pubmed
  6. Johnson K, Mahajan S, Wilson A. Herpes simplex virus transactivator VP16 discriminates between HCF-1 and a novel family member, HCF-2. J Virol. 1999;73:3930-40 pubmed
    ..Implications for regulation of the viral life cycle are discussed. ..
  7. Narayanan A, Ruyechan W, Kristie T. The coactivator host cell factor-1 mediates Set1 and MLL1 H3K4 trimethylation at herpesvirus immediate early promoters for initiation of infection. Proc Natl Acad Sci U S A. 2007;104:10835-40 pubmed
    ..These studies also contribute to the model whereby the induced nuclear transport of HCF-1 in sensory neurons may be critical to the reactivation of latent herpesviruses by promoting the activation of chromatin modifications. ..
  8. Whitlow Z, Kristie T. Recruitment of the transcriptional coactivator HCF-1 to viral immediate-early promoters during initiation of reactivation from latency of herpes simplex virus type 1. J Virol. 2009;83:9591-5 pubmed publisher
    ..The data support the model whereby HCF-1 plays a pivotal role in the reactivation of HSV-1 from latency...
  9. Dejosez M, Levine S, Frampton G, Whyte W, Stratton S, Barton M, et al. Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells. Genes Dev. 2010;24:1479-84 pubmed publisher
    ..We propose that Ronin/Hcf-1 controls a genetic program that contributes to the unimpeded growth of ES cells. ..
  10. Liu W, Tanasa B, Tyurina O, Zhou T, Gassmann R, Liu W, et al. PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression. Nature. 2010;466:508-12 pubmed publisher
    ..Thus, the identification and characterization of an H4K20me1 demethylase, PHF8, has revealed an intimate link between this enzyme and two distinct events in cell cycle progression. ..
  11. Eletr Z, Wilkinson K. An emerging model for BAP1's role in regulating cell cycle progression. Cell Biochem Biophys. 2011;60:3-11 pubmed publisher
    ..Given the robust associations between BAP1/HCF-1 and HCF-1/E2Fs, it is reasonable to speculate that BAP1 influences cell proliferation at G1/S by co-regulating transcription from HCF-1/E2F-governed promoters. ..
  12. Izeta A, Malcomber S, O Rourke D, Hodgkin J, O Hare P. A C-terminal targeting signal controls differential compartmentalisation of Caenorhabditis elegans host cell factor (HCF) to the nucleus or mitochondria. Eur J Cell Biol. 2003;82:495-504 pubmed
    ..This novel targeting signal is sufficient to redirect HCF-2 into mitochondria. It can also be transferred to an unrelated protein, resulting in its targeting to both the mitochondrial and nuclear compartments. ..
  13. Luciano R, Wilson A. HCF-1 functions as a coactivator for the zinc finger protein Krox20. J Biol Chem. 2003;278:51116-24 pubmed
    ..These results suggest that HCF-1 is recruited by many different classes of cellular transcription factors and is therefore likely to be required for a variety of cellular processes including cell cycle progression and development. ..
  14. Mahajan S, Little M, Vazquez R, Wilson A. Interaction of HCF-1 with a cellular nuclear export factor. J Biol Chem. 2002;277:44292-9 pubmed
    ..These data suggest that HPIP regulates HCF-1 activity by modulating its subcellular localization. Furthermore, HPIP-mediated export may provide the pool of cytoplasmic HCF-1 required for import of virion-derived VP16 into the nucleus. ..
  15. Wysocka J, Herr W. The herpes simplex virus VP16-induced complex: the makings of a regulatory switch. Trends Biochem Sci. 2003;28:294-304 pubmed
    ..The activities of Oct-1 and HCF-1 - two important regulators of cellular gene expression and proliferation - illuminate strategies by which HSV might coexist with its host. ..
  16. Narayanan A, Nogueira M, Ruyechan W, Kristie T. Combinatorial transcription of herpes simplex virus and varicella zoster virus immediate early genes is strictly determined by the cellular coactivator HCF-1. J Biol Chem. 2005;280:1369-75 pubmed
    ..The requirements for this protein supports the model whereby the regulated transport of HCF-1 from the cytoplasm to the nucleus in sensory neurons may control IE gene expression and reactivation of these viruses from the latent state. ..
  17. Yokoyama A, Wang Z, Wysocka J, Sanyal M, Aufiero D, Kitabayashi I, et al. Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression. Mol Cell Biol. 2004;24:5639-49 pubmed
    ..These studies link the menin tumor suppressor protein with the MLL histone methyltransferase machinery, with implications for Hox gene expression in development and leukemia pathogenesis. ..
  18. Parker J, Palchaudhuri S, Yin H, Wei J, Chakravarti D. A transcriptional regulatory role of the THAP11-HCF-1 complex in colon cancer cell function. Mol Cell Biol. 2012;32:1654-70 pubmed publisher
  19. Kristie T, Pomerantz J, Twomey T, Parent S, Sharp P. The cellular C1 factor of the herpes simplex virus enhancer complex is a family of polypeptides. J Biol Chem. 1995;270:4387-94 pubmed
    ..Although the C1 factor appears to be ubiquitously expressed, it is localized to subnuclear structures in specific cell types. ..
  20. Reilly P, Wysocka J, Herr W. Inactivation of the retinoblastoma protein family can bypass the HCF-1 defect in tsBN67 cell proliferation and cytokinesis. Mol Cell Biol. 2002;22:6767-78 pubmed
    ..These results suggest that HCF-1 regulates mammalian-cell proliferation and cytokinesis, at least in part, by either directly or indirectly opposing pRb family member function. ..
  21. Goto H, Motomura S, Wilson A, Freiman R, Nakabeppu Y, Fukushima K, et al. A single-point mutation in HCF causes temperature-sensitive cell-cycle arrest and disrupts VP16 function. Genes Dev. 1997;11:726-37 pubmed
    ..The finding that the same point mutation in HCF disrupts both VP16 function and the cell cycle suggests that HCF plays a role in cell-cycle progression in addition to VP16-dependent transcription...
  22. Gunther M, Laithier M, Brison O. A set of proteins interacting with transcription factor Sp1 identified in a two-hybrid screening. Mol Cell Biochem. 2000;210:131-42 pubmed
    ..Four other cDNA clones encoding polypeptides of unknown function were tested in the in vitro binding assay. All four polypeptides were found to interact with Sp1 in this assay. ..
  23. Freiman R, Herr W. Viral mimicry: common mode of association with HCF by VP16 and the cellular protein LZIP. Genes Dev. 1997;11:3122-7 pubmed
    ..The LZIP-related Drosophila protein BBF-2/dCREB-A contains this HCF-binding motif, indicating that the LZIP-HCF interaction has been conserved during metazoan evolution. ..
  24. Lu R, Misra V. Potential role for luman, the cellular homologue of herpes simplex virus VP16 (alpha gene trans-inducing factor), in herpesvirus latency. J Virol. 2000;74:934-43 pubmed
    ..Interestingly, Luman could activate the promoters of IE110 and LAT, two genes that are critical for reactivation of HSV-1 from latency. This suggests a role for Luman in the reactivation process as well. ..
  25. Kristie T, Vogel J, Sears A. Nuclear localization of the C1 factor (host cell factor) in sensory neurons correlates with reactivation of herpes simplex virus from latency. Proc Natl Acad Sci U S A. 1999;96:1229-33 pubmed
    ..The regulated localization suggests that C1 is a critical switch determinant of the viral lytic-latent cycle. ..
  26. Deplus R, Delatte B, Schwinn M, Defrance M, Méndez J, Murphy N, et al. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J. 2013;32:645-55 pubmed publisher
    ..Together, our results unveil a step-wise model, involving TET-OGT interactions, promotion of GlcNAcylation, and influence on H3K4me3 via SET1/COMPASS, highlighting a novel means by which TETs may induce transcriptional activation. ..
  27. Lu R, Yang P, O Hare P, Misra V. Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16-associated host cellular factor. Mol Cell Biol. 1997;17:5117-26 pubmed
    ..Luman appears to be a ubiquitous transcription factor, and its mRNA was detected in all human adult and fetal tissues examined. The possible role of HCF in regulating the function of this ubiquitous transcription factor is discussed. ..
  28. Vercauteren K, Gleyzer N, Scarpulla R. PGC-1-related coactivator complexes with HCF-1 and NRF-2beta in mediating NRF-2(GABP)-dependent respiratory gene expression. J Biol Chem. 2008;283:12102-11 pubmed publisher
    ..These changes in gene expression coincide with a marked reduction in cytochrome oxidase activity. The results are consistent with a pathway whereby PRC regulates NRF-2-dependent genes through a multiprotein complex involving HCF-1. ..
  29. Mahajan S, Wilson A. Mutations in host cell factor 1 separate its role in cell proliferation from recruitment of VP16 and LZIP. Mol Cell Biol. 2000;20:919-28 pubmed
  30. Vogel J, Kristie T. Site-specific proteolysis of the transcriptional coactivator HCF-1 can regulate its interaction with protein cofactors. Proc Natl Acad Sci U S A. 2006;103:6817-22 pubmed
    ..This paradigm expands the biological significance of limited proteolytic processing as a regulatory mechanism in gene transcription. ..
  31. Reilly P, Herr W. Spontaneous reversion of tsBN67 cell proliferation and cytokinesis defects in the absence of HCF-1 function. Exp Cell Res. 2002;277:119-30 pubmed
    ..The revertant tsBN67 cells display a coincident restoration of cell proliferation and suppression of the cytokinetic defect, suggesting that HCF-1 plays a shared role in cell proliferation and cytokinesis. ..
  32. Ajuh P, Browne G, Hawkes N, Cohen P, Roberts S, Lamond A. Association of a protein phosphatase 1 activity with the human factor C1 (HCF) complex. Nucleic Acids Res. 2000;28:678-86 pubmed
    ..The data suggest novel roles for HCF and PP1, which may be relevant to their functions in transcription and cell cycle progression. ..
  33. Vogel J, Kristie T. The novel coactivator C1 (HCF) coordinates multiprotein enhancer formation and mediates transcription activation by GABP. EMBO J. 2000;19:683-90 pubmed
    ..The interaction and coordinated assembly of the enhancer proteins by the C1 factor may be critical for the regulation of the HSV lytic-latent cycle. ..
  34. Capotosti F, Guernier S, Lammers F, Waridel P, Cai Y, Jin J, et al. O-GlcNAc transferase catalyzes site-specific proteolysis of HCF-1. Cell. 2011;144:376-88 pubmed publisher
    ..These results reveal an unexpected role of OGT in HCF-1 proteolytic maturation and an unforeseen nexus between OGT-directed O-GlcNAcylation and proteolytic maturation in HCF-1 cell-cycle regulation. ..
  35. Julien E, Herr W. Proteolytic processing is necessary to separate and ensure proper cell growth and cytokinesis functions of HCF-1. EMBO J. 2003;22:2360-9 pubmed
    ..These results suggest that HCF-1 links the regulation of exit from mitosis and the G(1) phase of cell growth, possibly to coordinate the reactivation of gene expression after mitosis. ..
  36. Yu H, Mashtalir N, Daou S, Hammond Martel I, Ross J, Sui G, et al. The ubiquitin carboxyl hydrolase BAP1 forms a ternary complex with YY1 and HCF-1 and is a critical regulator of gene expression. Mol Cell Biol. 2010;30:5071-85 pubmed publisher
    ..Our findings (i) establish a direct link between BAP1 and the transcriptional control of genes regulating cell growth and proliferation and (ii) shed light on a novel mechanism of transcription regulation involving ubiquitin signaling. ..
  37. Wilson A, Freiman R, Goto H, Nishimoto T, Herr W. VP16 targets an amino-terminal domain of HCF involved in cell cycle progression. Mol Cell Biol. 1997;17:6139-46 pubmed
    ..Rescue of the tsBN67 cell proliferation defect by HCF, however, requires both the VP16 interaction domain and an adjacent basic region, indicating that HCF utilizes multiple regions to promote cell cycle progression. ..
  38. Tyagi S, Herr W. E2F1 mediates DNA damage and apoptosis through HCF-1 and the MLL family of histone methyltransferases. EMBO J. 2009;28:3185-95 pubmed publisher
    ..Indeed, sequence changes in the E2F1 HCF-1-binding site can modulate both up and down the ability of E2F1 to induce apoptosis indicating that HCF-1 association with E2F1 is a regulator of E2F1-induced apoptosis. ..
  39. Machida Y, Machida Y, Vashisht A, Wohlschlegel J, Dutta A. The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1. J Biol Chem. 2009;284:34179-88 pubmed publisher
    ..These results suggest that BAP1 regulates cell proliferation by deubiquitinating HCF-1. ..
  40. Cai Y, Jin J, Swanson S, Cole M, Choi S, Florens L, et al. Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex. J Biol Chem. 2010;285:4268-72 pubmed publisher
    ..Although MSL-associated MOF acetylates nucleosomal histone H4 almost exclusively on lysine 16, NSL-associated MOF exhibits a relaxed specificity and also acetylates nucleosomal histone H4 on lysines 5 and 8. ..
  41. Mazars R, Gonzalez de Peredo A, Cayrol C, Lavigne A, Vogel J, Ortega N, et al. The THAP-zinc finger protein THAP1 associates with coactivator HCF-1 and O-GlcNAc transferase: a link between DYT6 and DYT3 dystonias. J Biol Chem. 2010;285:13364-71 pubmed publisher
    ..Interestingly, our results also provide an unexpected link between DYT6 and DYT3 (X-linked dystonia-parkinsonism) dystonias because the gene encoding the THAP1/DYT6 protein partner OGT maps within the DYT3 critical region on Xq13.1. ..
  42. Mahajan S, Johnson K, Wilson A. Molecular cloning of Drosophila HCF reveals proteolytic processing and self-association of the encoded protein. J Cell Physiol. 2003;194:117-26 pubmed
    ..The conservation of HCF processing in insect cells argues that formation of separate N- and C-terminal subunits is important for HCF function. ..
  43. Luciano R, Wilson A. N-terminal transcriptional activation domain of LZIP comprises two LxxLL motifs and the host cell factor-1 binding motif. Proc Natl Acad Sci U S A. 2000;97:10757-62 pubmed
    ..The LxxLL motifs are not required for association with the HCF-1 beta-propeller and instead interact with other regions in HCF-1 or recruit additional cofactors. ..
  44. Lu R, Misra V. Zhangfei: a second cellular protein interacts with herpes simplex virus accessory factor HCF in a manner similar to Luman and VP16. Nucleic Acids Res. 2000;28:2446-54 pubmed
    ..The ability of ZF to block the synthesis of the HSV IE protein ICP0 relied on its binding to HCF, since a mutant of ZF that was unable to bind HCF was also unable to prevent viral IE protein expression. ..
  45. Peng H, Nogueira M, Vogel J, Kristie T. Transcriptional coactivator HCF-1 couples the histone chaperone Asf1b to HSV-1 DNA replication components. Proc Natl Acad Sci U S A. 2010;107:2461-6 pubmed publisher
    ..This coupling provides a novel function for HCF-1 and insights into the mechanisms of modulating chromatin during DNA replication...
  46. Liang Y, Vogel J, Narayanan A, Peng H, Kristie T. Inhibition of the histone demethylase LSD1 blocks alpha-herpesvirus lytic replication and reactivation from latency. Nat Med. 2009;15:1312-7 pubmed publisher
    ..The results support pharmaceutical control of histone modifying enzymes as a strategy for controlling herpesvirus infections...
  47. Kristie T, Liang Y, Vogel J. Control of alpha-herpesvirus IE gene expression by HCF-1 coupled chromatin modification activities. Biochim Biophys Acta. 2010;1799:257-65 pubmed publisher
    ..Strikingly, the absence of HCF-1 results in the accumulation of nucleosomes bearing repressive marks on the viral IE promoters and silencing of viral gene expression. ..
  48. Lu R, Yang P, Padmakumar S, Misra V. The herpesvirus transactivator VP16 mimics a human basic domain leucine zipper protein, luman, in its interaction with HCF. J Virol. 1998;72:6291-7 pubmed
    ..These data suggest that the HCF-Luman interaction may represent a conserved mechanism for transcriptional regulation in metazoans, and HSV mimics this interaction with HCF to monitor the physiological state of the host cell. ..
  49. Dejosez M, Krumenacker J, Zitur L, Passeri M, Chu L, Songyang Z, et al. Ronin is essential for embryogenesis and the pluripotency of mouse embryonic stem cells. Cell. 2008;133:1162-74 pubmed publisher
    ..Our findings identify Ronin as an essential factor underlying embryogenesis and ES cell pluripotency. Its association with HCF-1 suggests an epigenetic mechanism of gene repression in pluripotent cells. ..
  50. Lee S, Horn V, Julien E, Liu Y, Wysocka J, Bowerman B, et al. Epigenetic regulation of histone H3 serine 10 phosphorylation status by HCF-1 proteins in C. elegans and mammalian cells. PLoS ONE. 2007;2:e1213 pubmed
    ..Mammalian cells with defective HCF-1 also display defects in mitotic H3S10P status. These results suggest that HCF-1 proteins possess conserved roles in the regulation of cell division and mitotic histone phosphorylation. ..
  51. Delehouzee S, Yoshikawa T, Sawa C, Sawada J, Ito T, Omori M, et al. GABP, HCF-1 and YY1 are involved in Rb gene expression during myogenesis. Genes Cells. 2005;10:717-31 pubmed
    ..These results indicate that the Rb promoter is subject to regulation by positive and negative factors and that this intricate activation mechanism is critical to allow the accurate Rb gene up-regulation observed during myogenesis. ..
  52. Neumann M, Fries H, Scheicher C, Keikavoussi P, Kolb Mäurer A, Brocker E, et al. Differential expression of Rel/NF-kappaB and octamer factors is a hallmark of the generation and maturation of dendritic cells. Blood. 2000;95:277-85 pubmed
    ..Blood. 2000;95:277-285) ..
  53. Ruzek M, O Brien D, Mathur A. Decreased production of IL-2 and IFN-gamma by stimulated splenocytes from mice bearing plasma cell tumors is associated with alteration of DNA-binding factors. Int Immunol. 1996;8:1971-82 pubmed
    ..These results suggest that PCT induce changes in certain transcription factors that are important for anti-tumor responses, including T cell proliferative responses and Th1-associated cytokine production. ..