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Gene Review

HCFC1  -  host cell factor C1

Homo sapiens

Synonyms: C1 factor, CFF, HCF, HCF-1, HCF1, ...
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Disease relevance of HCFC1

  • The determined transcribed sequence from a human fetal brain library is identical to that of the recently identified accessory protein HCFC1 (host cell factor, also called C1) that activates herpes simplex virus VP16 (alpha TIF) transactivator protein for association with the octamer motif-binding protein Oct-1 (Cell 74: 115, 1993) [1].
  • Host cell factor (HCF) was initially discovered as a cellular co-factor required for the activation of herpes simplex virus immediate early gene expression by the virion associated transactivator VP16 [2].
  • HCF-1 was also found to be essential for the induction of varicella zoster virus IE gene expression by ORF10, the VZV ortholog of the HSV IE transactivator VP16, and the autostimulatory IE62 protein [3].
  • VP16 forms a complex with cellular factors (Oct1 and host cell factor [HCF]) and TAATGARAT elements (found in all HSV-1 IE promoter/enhancer sequences) to mediate stimulation of IE transcription [4].
  • Our objective is to explore interactions between Luman and HCF and to determine if they play a role in the biology of herpesviruses [5].

Psychiatry related information on HCFC1

  • The effects of the compounds were evaluated by objective tests (Buschke selective reminding test, CFF, simple reaction time, tapping, arithmetical calculation) and subjective measurements (visual analogue scale, side effects questionnaire) [6].
  • OBJECTIVE: To describe child- and family-focused cognitive-behavioral therapy (CFF-CBT), a new developmentally sensitive psychosocial intervention for pediatric bipolar disorder (PBD) that is intended for use along with medication [7].
  • In contrast, a single dose of midazolam 15 mg induced a marked impairment in psychomotor performance and cognitive functions (significant reduction in CFF, increase in CRT and body sway, disruption of short- and long-term memory) [8].
  • After 0.2 mg Ro 16-6028 a decrease of attention, numerical memory, psychomotor activity, wakefulness and CFF was observed, while mood improved at later time periods outlasting the sedation [9].
  • Implications of the modified scotoma hypothesis are discussed for (1) the neutral-density-filter test to distinguish functional from organic amblyopia, (2) the reduced CFF threshold for amblyopic eyes, (3) expectations of stereopsis for amblyopes, and (4) possible mechanisms for amblyopia [10].

High impact information on HCFC1

  • Upon lytic infection of permissive cells, the herpes simplex virus (HSV) transactivator protein VP16 associates with an accessory protein termed host cell factor (HCF) [11].
  • Binding to HCF activates VP16 for association with the octamer motif-binding protein Oct-1, to form a multiprotein-DNA complex responsible for activating transcription of the HSV immediate early genes [11].
  • 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 [11].
  • Although there is no obvious sequence similarity between HCF and other known proteins, HCF contains eight repeats of a new 26 amino acid motif. cDNAs encoding HCF predict a large open reading frame of 2035 codons [11].
  • HCF-1 tethers the Sin3 and Set1/Ash2 transcriptional regulatory complexes together even though they are generally associated with opposite transcriptional outcomes: repression and activation of transcription, respectively [12].

Chemical compound and disease context of HCFC1


Biological context of HCFC1


Anatomical context of HCFC1


Associations of HCFC1 with chemical compounds


Physical interactions of HCFC1

  • We have shown that the highly conserved C-terminal WYF domain of HCF-1 protein interacts with the MYND domain of the PDCD2 protein [24].
  • Here we report a second human protein, Zhangfei (ZF) that interacts with HCF in a fashion similar to Luman and VP16 [28].
  • We show here that E2F4 specifically and directly interacts with HCF-1 [29].
  • Luman and VP16 appear to have similar mechanisms for binding HCF, as in vitro each competitively inhibited the binding of the other to HCF [30].
  • In cells, FHL2 interacts exclusively with the nonprocessed coactivator and costimulates transcription of an HCF-1-dependent target gene [31].

Regulatory relationships of HCFC1

  • Importantly, with several of the mutants we observe a poor correlation between the ability to associate with LZIP and promote cell proliferation in the context of the full HCF-1 amino terminus, arguing that the HCF-1 beta-propeller domain must target other cellular transcription factors in order to contribute to G(1) progression [19].
  • These data suggest that HPIP regulates HCF-1 activity by modulating its subcellular localization [20].
  • Mutations in the HCF-1 kelch domain known to block cell growth abrogated E2F4 binding to the kelch domain in the absence but not in the presence of the juxtaposed basic region [29].
  • HCF binds directly to VP16 and this promotes subsequent interaction of the VP16-HCF complex with the POU DNA-binding domain of Oct-1 and selective assembly onto target sites [32].
  • The functional interaction of HCF-1 with FHL2 supports a model in which site-specific proteolysis regulates the interaction of HCF-1 with protein partners and thus can modulate the activity of this coactivator [31].

Other interactions of HCFC1

  • Furthermore, HPIP-mediated export may provide the pool of cytoplasmic HCF-1 required for import of virion-derived VP16 into the nucleus [20].
  • The complete sequence of the host cell factor 1 (HCFC1) gene and its promoter: a role for YY1 transcription factor in the regulation of its expression [18].
  • This inter-action is conserved between human HCF-1 and HCF-2 and the C. elegans HCF [24].
  • The herpesvirus transactivator VP16 mimics a human basic domain leucine zipper protein, luman, in its interaction with HCF [33].
  • Mutational analysis showed E2F4 independently targets the kelch domain and the basic domain (residues 450-902) of HCF-1, both of which are required for normal cell-cycle progression via separate determinants [29].

Analytical, diagnostic and therapeutic context of HCFC1


  1. Genomic organization of the human VP16 accessory protein, a housekeeping gene (HCFC1) mapping to Xq28. Frattini, A., Faranda, S., Redolfi, E., Zucchi, I., Villa, A., Patrosso, M.C., Strina, D., Susani, L., Vezzoni, P. Genomics (1994) [Pubmed]
  2. Zhangfei is a potent and specific inhibitor of the host cell factor-binding transcription factor Luman. Misra, V., Rapin, N., Akhova, O., Bainbridge, M., Korchinski, P. J. Biol. Chem. (2005) [Pubmed]
  3. Combinatorial transcription of herpes simplex virus and varicella zoster virus immediate early genes is strictly determined by the cellular coactivator HCF-1. Narayanan, A., Nogueira, M.L., Ruyechan, W.T., Kristie, T.M. J. Biol. Chem. (2005) [Pubmed]
  4. Proteins and cis-acting elements associated with transactivation of the varicella-zoster virus (VZV) immediate-early gene 62 promoter by VZV open reading frame 10 protein. Moriuchi, H., Moriuchi, M., Cohen, J.I. J. Virol. (1995) [Pubmed]
  5. Potential role for luman, the cellular homologue of herpes simplex virus VP16 (alpha gene trans-inducing factor), in herpesvirus latency. Lu, R., Misra, V. J. Virol. (2000) [Pubmed]
  6. Study of the potential reversal of triazolam memory and cognitive deficits by RU 41 656 in healthy subjects. Patat, A., Klein, M.J., Surjus, A., Hucher, M., Granier, J. Psychopharmacology (Berl.) (1991) [Pubmed]
  7. Child- and family-focused cognitive-behavioral therapy for pediatric bipolar disorder: development and preliminary results. Pavuluri, M.N., Graczyk, P.A., Henry, D.B., Carbray, J.A., Heidenreich, J., Miklowitz, D.J. Journal of the American Academy of Child and Adolescent Psychiatry. (2004) [Pubmed]
  8. Lack of amnestic, psychotomimetic or impairing effect on psychomotor performance of eliprodil, a new NMDA antagonist. Patat, A., Molinier, P., Hergueta, T., Brohier, S., Zieleniuk, I., Danjou, P., Warot, D., Puech, A. International clinical psychopharmacology. (1994) [Pubmed]
  9. On the central effects of a new partial benzodiazepine agonist Ro 16-6028 in man: pharmaco-EEG and psychometric studies. Saletu, B., Grünberger, J., Linzmayer, L. International journal of clinical pharmacology, therapy, and toxicology. (1989) [Pubmed]
  10. Monocular performance of functional amblyopes: another look at the scotoma hypothesis. Higgins, K.E. American journal of optometry and physiological optics. (1978) [Pubmed]
  11. The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein. Wilson, A.C., LaMarco, K., Peterson, M.G., Herr, W. Cell (1993) [Pubmed]
  12. Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Wysocka, J., Myers, M.P., Laherty, C.D., Eisenman, R.N., Herr, W. Genes Dev. (2003) [Pubmed]
  13. A single-point mutation in HCF causes temperature-sensitive cell-cycle arrest and disrupts VP16 function. Goto, H., Motomura, S., Wilson, A.C., Freiman, R.N., Nakabeppu, Y., Fukushima, K., Fujishima, M., Herr, W., Nishimoto, T. Genes Dev. (1997) [Pubmed]
  14. High-carbohydrate, high-fiber diets for insulin-treated men with diabetes mellitus. Anderson, J.W., Ward, K. Am. J. Clin. Nutr. (1979) [Pubmed]
  15. Expression and mutational analysis of Autographa californica nucleopolyhedrovirus HCF-1: functional requirements for cysteine residues. Wilson, J.A., Forney, S.D., Ricci, A.M., Allen, E.G., Hefferon, K.L., Miller, L.K. J. Virol. (2005) [Pubmed]
  16. Effects of a sedative and of a non-sedative H1-antihistamine on the event-related potential (ERP) in normal volunteers. Swire, F.M., Marsden, C.A., Barber, C., Birmingham, A.T. Psychopharmacology (Berl.) (1989) [Pubmed]
  17. Acute behavioral effects of exposure to some organic solvents -psychophysiological aspects. Winneke, G. Acta Neurol. Scand., Suppl. (1982) [Pubmed]
  18. The complete sequence of the host cell factor 1 (HCFC1) gene and its promoter: a role for YY1 transcription factor in the regulation of its expression. Zoppè, M., Frattini, A., Faranda, S., Vezzoni, P. Genomics (1996) [Pubmed]
  19. Mutations in host cell factor 1 separate its role in cell proliferation from recruitment of VP16 and LZIP. Mahajan, S.S., Wilson, A.C. Mol. Cell. Biol. (2000) [Pubmed]
  20. Interaction of HCF-1 with a cellular nuclear export factor. Mahajan, S.S., Little, M.M., Vazquez, R., Wilson, A.C. J. Biol. Chem. (2002) [Pubmed]
  21. HCF-1 functions as a coactivator for the zinc finger protein Krox20. Luciano, R.L., Wilson, A.C. J. Biol. Chem. (2003) [Pubmed]
  22. The gene encoding the VP16-accessory protein HCF (HCFC1) resides in human Xq28 and is highly expressed in fetal tissues and the adult kidney. Wilson, A.C., Parrish, J.E., Massa, H.F., Nelson, D.L., Trask, B.J., Herr, W. Genomics (1995) [Pubmed]
  23. A novel 50-kilodalton fragment of host cell factor 1 (C1) in G(0) cells. Scarr, R.B., Smith, M.R., Beddall, M., Sharp, P.A. Mol. Cell. Biol. (2000) [Pubmed]
  24. PDCD2 is a negative regulator of HCF-1 (C1). Scarr, R.B., Sharp, P.A. Oncogene (2002) [Pubmed]
  25. The HCF repeat is an unusual proteolytic cleavage signal. Wilson, A.C., Peterson, M.G., Herr, W. Genes Dev. (1995) [Pubmed]
  26. A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1. Julien, E., Herr, W. Mol. Cell (2004) [Pubmed]
  27. VP16 targets an amino-terminal domain of HCF involved in cell cycle progression. Wilson, A.C., Freiman, R.N., Goto, H., Nishimoto, T., Herr, W. Mol. Cell. Biol. (1997) [Pubmed]
  28. Zhangfei: a second cellular protein interacts with herpes simplex virus accessory factor HCF in a manner similar to Luman and VP16. Lu, R., Misra, V. Nucleic Acids Res. (2000) [Pubmed]
  29. Host Cell Factor-1 and E2F4 Interact Via Multiple Determinants in Each Protein. Knez, J., Piluso, D., Bilan, P., Capone, J.P. Mol. Cell. Biochem. (2006) [Pubmed]
  30. Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16-associated host cellular factor. Lu, R., Yang, P., O'Hare, P., Misra, V. Mol. Cell. Biol. (1997) [Pubmed]
  31. Site-specific proteolysis of the transcriptional coactivator HCF-1 can regulate its interaction with protein cofactors. Vogel, J.L., Kristie, T.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  32. HCF-dependent nuclear import of VP16. La Boissière, S., Hughes, T., O'Hare, P. EMBO J. (1999) [Pubmed]
  33. The herpesvirus transactivator VP16 mimics a human basic domain leucine zipper protein, luman, in its interaction with HCF. Lu, R., Yang, P., Padmakumar, S., Misra, V. J. Virol. (1998) [Pubmed]
  34. Protein interactions in the herpes simplex virus type 1 VP16-induced complex: VP16 peptide inhibition and mutational analysis of host cell factor requirements. Simmen, K.A., Newell, A., Robinson, M., Mills, J.S., Canning, G., Handa, R., Parkes, K., Borkakoti, N., Jupp, R. J. Virol. (1997) [Pubmed]
  35. Contribution of VCAF-positive cells to neovascularization and calcification in atherosclerotic plaque development. Wilkinson, F., Liu, Y., Rucka, A., Jeziorska, M., Hoyland, J., Heagerty, A., Canfield, A., Alexander, M. J. Pathol. (2007) [Pubmed]
  36. High-carbohydrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults. Fukagawa, N.K., Anderson, J.W., Hageman, G., Young, V.R., Minaker, K.L. Am. J. Clin. Nutr. (1990) [Pubmed]
  37. Comparison of calculated and measured heterogeneity correction factors for 125I, 137Cs, and 192Ir brachytherapy sources near localized heterogeneities. Williamson, J.F., Perera, H., Li, Z., Lutz, W.R. Medical physics. (1993) [Pubmed]
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