Host cell factor C1 explained

Host cell factor 1 (HCFC1, HCF1, or HCF-1), also known as VP16-accessory protein,^[1] is a protein that in humans is encoded by the HCFC1 gene.^{[2] [3]}

Structure

HCF1 is a member of the highly conserved host cell factor family and encodes a protein with five Kelch repeats, a fibronectin-like motif, and six HCF repeats, each of which contains a highly specific cleavage signal. This nuclear transcription coregulator is proteolytically cleaved at one or more of the six possible sites, resulting in the creation of an N-terminal chain and the corresponding C-terminal chain. The final form of this protein consists of noncovalently bound N- and C-terminal chains which interact through electrostatic forces.

Function

HCF1 is involved in control of the cell cycle as well as having regulatory roles in a multitude of processes related to transcription. Additionally, work in model organisms point to HCF1 as being a putative longevity determinant.^[4] Alternatively spliced variants that encode different protein isoforms have been described; however, not all variants have been fully characterized.^[3]

Mutations in this gene have been linked to disorders of the cobalamine metabolism.^[5]

Interactions

Host cell factor C1 has been shown to interact with:

• BAP1,^[6]
• CREB3,^{[7] [8]}
• GABPA,^[9]
• HDAC1,^[10]
• HDAC2,^[10]
• MLL,
• OGT,^[10]
• PDCD2,^[11]
• POU2F1,^{[12] [13]}
• PPP1CA,^[14]
• SIN3A,^{[10] [15]}
• SP1,^{[10] [16]}
• SUDS3,^[10]
• WDR5,^{[10] [15]} and
• ZBTB17.^[17]

Further reading

• Oehler T, Angel P . A common intermediary factor (p52/54) recognizing "acidic blob"-type domains is required for transcriptional activation by the Jun proteins . Molecular and Cellular Biology . 12 . 12 . 5508–15 . Dec 1992 . 1448082 . 360488 . 10.1128/mcb.12.12.5508.
• Wilson AC, Peterson MG, Herr W . The HCF repeat is an unusual proteolytic cleavage signal . Genes & Development . 9 . 20 . 2445–58 . Oct 1995 . 7590226 . 10.1101/gad.9.20.2445 . free .
• Klemm RD, Goodrich JA, Zhou S, Tjian R . Molecular cloning and expression of the 32-kDa subunit of human TFIID reveals interactions with VP16 and TFIIB that mediate transcriptional activation . Proceedings of the National Academy of Sciences of the United States of America . 92 . 13 . 5788–92 . Jun 1995 . 7597030 . 41586 . 10.1073/pnas.92.13.5788 . 1995PNAS...92.5788K . free .
• Frattini A, Faranda S, Redolfi E, Zucchi I, Villa A, Patrosso MC, Strina D, Susani L, Vezzoni P . Genomic organization of the human VP16 accessory protein, a housekeeping gene (HCFC1) mapping to Xq28 . Genomics . 23 . 1 . 30–5 . Sep 1994 . 7829097 . 10.1006/geno.1994.1455 .
• Kristie TM, Pomerantz JL, Twomey TC, Parent SA, Sharp PA . The cellular C1 factor of the herpes simplex virus enhancer complex is a family of polypeptides . The Journal of Biological Chemistry . 270 . 9 . 4387–94 . Mar 1995 . 7876203 . 10.1074/jbc.270.9.4387 . free .
• Kristie TM, Sharp PA . 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) . The Journal of Biological Chemistry . 268 . 9 . 6525–34 . Mar 1993 . 10.1016/S0021-9258(18)53282-8 . 8454622 . free .
• Zoppè M, Frattini A, Faranda S, Vezzoni P . 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 . Genomics . 34 . 1 . 85–91 . May 1996 . 8661027 . 10.1006/geno.1996.0244 .
• Wilson AC, Freiman RN, Goto H, Nishimoto T, Herr W . VP16 targets an amino-terminal domain of HCF involved in cell cycle progression . Molecular and Cellular Biology . 17 . 10 . 6139–46 . Oct 1997 . 9315674 . 232464 . 10.1128/mcb.17.10.6139.
• Freiman RN, Herr W . Viral mimicry: common mode of association with HCF by VP16 and the cellular protein LZIP . Genes & Development . 11 . 23 . 3122–7 . Dec 1997 . 9389645 . 316754 . 10.1101/gad.11.23.3122 .
• 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 . Journal of Virology . 72 . 8 . 6291–7 . Aug 1998 . 9658067 . 109766 . 10.1128/JVI.72.8.6291-6297.1998.
• Ge H, Si Y, Roeder RG . Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation . The EMBO Journal . 17 . 22 . 6723–9 . Nov 1998 . 9822615 . 1171017 . 10.1093/emboj/17.22.6723 .
• La Boissière S, Hughes T, O'Hare P . HCF-dependent nuclear import of VP16 . The EMBO Journal . 18 . 2 . 480–9 . Jan 1999 . 9889203 . 1171141 . 10.1093/emboj/18.2.480 .
• Lu R, Misra V . Potential role for luman, the cellular homologue of herpes simplex virus VP16 (alpha gene trans-inducing factor), in herpesvirus latency . Journal of Virology . 74 . 2 . 934–43 . Jan 2000 . 10623756 . 111614 . 10.1128/JVI.74.2.934-943.2000 .
• Mahajan SS, Wilson AC . Mutations in host cell factor 1 separate its role in cell proliferation from recruitment of VP16 and LZIP . Molecular and Cellular Biology . 20 . 3 . 919–28 . Feb 2000 . 10629049 . 85209 . 10.1128/MCB.20.3.919-928.2000 .
• Ajuh PM, Browne GJ, Hawkes NA, Cohen PT, Roberts SG, Lamond AI . Association of a protein phosphatase 1 activity with the human factor C1 (HCF) complex . Nucleic Acids Research . 28 . 3 . 678–86 . Feb 2000 . 10637318 . 102561 . 10.1093/nar/28.3.678 .
• Vogel JL, Kristie TM . The novel coactivator C1 (HCF) coordinates multiprotein enhancer formation and mediates transcription activation by GABP . The EMBO Journal . 19 . 4 . 683–90 . Feb 2000 . 10675337 . 305606 . 10.1093/emboj/19.4.683 .
• Scarr RB, Smith MR, Beddall M, Sharp PA . A novel 50-kilodalton fragment of host cell factor 1 (C1) in G(0) cells . Molecular and Cellular Biology . 20 . 10 . 3568–75 . May 2000 . 10779346 . 85649 . 10.1128/MCB.20.10.3568-3575.2000 .
• Choi Y, Asada S, Uesugi M . Divergent hTAFII31-binding motifs hidden in activation domains . The Journal of Biological Chemistry . 275 . 21 . 15912–6 . May 2000 . 10821850 . 10.1074/jbc.275.21.15912 . free .
• 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 Research . 28 . 12 . 2446–54 . Jun 2000 . 10871379 . 102720 . 10.1093/nar/28.12.2446 .

Notes and References

1. http://genecards.org/cgi-bin/carddisp.pl?gene=HCFC1 GeneCards entry for HCFC1
2. Wilson AC, LaMarco K, Peterson MG, Herr W . The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein . Cell . 74 . 1 . 115–25 . Jul 1993 . 8392914 . 10.1016/0092-8674(93)90299-6 . 43569318 .
3. Web site: Entrez Gene: HCFC1 host cell factor C1 (VP16-accessory protein).
4. Li J, Ebata A, Dong Y, Rizki G, Iwata T, Lee SS . Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator . PLOS Biology . 6 . 9 . e233 . Sep 2008 . 18828672 . 2553839 . 10.1371/journal.pbio.0060233 . free .
5. Yu HC, Sloan JL, Scharer G, Brebner A, Quintana AM, Achilly NP, Manoli I, Coughlin CR, Geiger EA, Schneck U, Watkins D, Suormala T, Van Hove JL, Fowler B, Baumgartner MR, Rosenblatt DS, Venditti CP, Shaikh TH . An X-linked cobalamin disorder caused by mutations in transcriptional coregulator HCFC1 . American Journal of Human Genetics . 93 . 3 . 506–14 . Sep 2013 . 24011988 . 10.1016/j.ajhg.2013.07.022 . 3769968.
6. Machida YJ, Machida Y, Vashisht AA, Wohlschlegel JA, Dutta A . The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1 . The Journal of Biological Chemistry . 284 . 49 . 34179–88 . Dec 2009 . 19815555 . 2797188 . 10.1074/jbc.M109.046755 . free .
7. 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 . Journal of Virology . 72 . 8 . 6291–7 . Aug 1998 . 9658067 . 109766 . 10.1128/JVI.72.8.6291-6297.1998.
8. Freiman RN, Herr W . Viral mimicry: common mode of association with HCF by VP16 and the cellular protein LZIP . Genes & Development . 11 . 23 . 3122–7 . Dec 1997 . 9389645 . 316754 . 10.1101/gad.11.23.3122 .
9. Vogel JL, Kristie TM . The novel coactivator C1 (HCF) coordinates multiprotein enhancer formation and mediates transcription activation by GABP . The EMBO Journal . 19 . 4 . 683–90 . Feb 2000 . 10675337 . 305606 . 10.1093/emboj/19.4.683 .
10. Wysocka J, Myers MP, Laherty CD, Eisenman RN, 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 & Development . 17 . 7 . 896–911 . Apr 2003 . 12670868 . 196026 . 10.1101/gad.252103 .
11. Scarr RB, Sharp PA . PDCD2 is a negative regulator of HCF-1 (C1) . Oncogene . 21 . 34 . 5245–54 . Aug 2002 . 12149646 . 10.1038/sj.onc.1205647 . free .
12. La Boissière S, Hughes T, O'Hare P . HCF-dependent nuclear import of VP16 . The EMBO Journal . 18 . 2 . 480–9 . Jan 1999 . 9889203 . 1171141 . 10.1093/emboj/18.2.480 .
13. Kristie TM, Sharp PA . 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) . The Journal of Biological Chemistry . 268 . 9 . 6525–34 . Mar 1993 . 10.1016/S0021-9258(18)53282-8 . 8454622 . free .
14. Ajuh PM, Browne GJ, Hawkes NA, Cohen PT, Roberts SG, Lamond AI . Association of a protein phosphatase 1 activity with the human factor C1 (HCF) complex . Nucleic Acids Research . 28 . 3 . 678–86 . Feb 2000 . 10637318 . 102561 . 10.1093/nar/28.3.678 .
15. Yokoyama A, Wang Z, Wysocka J, Sanyal M, Aufiero DJ, Kitabayashi I, Herr W, Cleary ML . Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression . Molecular and Cellular Biology . 24 . 13 . 5639–49 . Jul 2004 . 15199122 . 480881 . 10.1128/MCB.24.13.5639-5649.2004 .
16. Gunther M, Laithier M, Brison O . A set of proteins interacting with transcription factor Sp1 identified in a two-hybrid screening . Molecular and Cellular Biochemistry . 210 . 1–2 . 131–42 . Jul 2000 . 10976766 . 10.1023/A:1007177623283 . 1339642 .
17. Piluso D, Bilan P, Capone JP . Host cell factor-1 interacts with and antagonizes transactivation by the cell cycle regulatory factor Miz-1 . The Journal of Biological Chemistry . 277 . 48 . 46799–808 . Nov 2002 . 12244100 . 10.1074/jbc.M206226200 . free .