| Structural highlights
Disease
HCFC1_HUMAN X-linked nonsyndromic intellectual deficit. Mental retardation, X-linked 3 (MRX3) [MIM:309541: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. Note=The disease is caused by mutations affecting the gene represented in this entry.[1]
Function
HCFC1_HUMAN Involved in control of the cell cycle. Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300. Coactivator for EGR2 and GABP2. Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription, respectively) together. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. In case of human herpes simplex virus (HSV) infection, HCFC1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and POU2F1 thereby enabling the transcription of the viral immediate early genes.[2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]
Publication Abstract from PubMed
Host-cell factor 1 (HCF-1) is an unusual transcriptional regulator that undergoes a process of proteolytic maturation to generate N- (HCF-1(N)) and C- (HCF-1(C)) terminal subunits noncovalently associated via self-association sequence elements. Here, we present the crystal structure of the self-association sequence 1 (SAS1) including the adjacent C-terminal HCF-1 nuclear localization signal (NLS). SAS1 elements from each of the HCF-1(N) and HCF-1(C) subunits form an interdigitated fibronectin type 3 (Fn3) tandem repeat structure. We show that the C-terminal NLS recruited by the interdigitated SAS1 structure is required for effective formation of a transcriptional regulatory complex: the herpes simplex virus VP16-induced complex. Thus, HCF-1(N)-HCF-1(C) association via an integrated Fn3 structure permits an NLS to facilitate formation of a transcriptional regulatory complex.
HCF-1 self-association via an interdigitated Fn3 structure facilitates transcriptional regulatory complex formation.,Park J, Lammers F, Herr W, Song JJ Proc Natl Acad Sci U S A. 2012 Oct 8. PMID:23045687[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Huang L, Jolly LA, Willis-Owen S, Gardner A, Kumar R, Douglas E, Shoubridge C, Wieczorek D, Tzschach A, Cohen M, Hackett A, Field M, Froyen G, Hu H, Haas SA, Ropers HH, Kalscheuer VM, Corbett MA, Gecz J. A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual disability. Am J Hum Genet. 2012 Oct 5;91(4):694-702. doi: 10.1016/j.ajhg.2012.08.011. Epub, 2012 Sep 20. PMID:23000143 doi:10.1016/j.ajhg.2012.08.011
- ↑ Vogel JL, Kristie TM. Autocatalytic proteolysis of the transcription factor-coactivator C1 (HCF): a potential role for proteolytic regulation of coactivator function. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9425-30. PMID:10920196 doi:10.1073/pnas.160266697
- ↑ Kristie TM, Vogel JL, Sears AE. 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 Feb 16;96(4):1229-33. PMID:9990006
- ↑ Vogel JL, Kristie TM. The novel coactivator C1 (HCF) coordinates multiprotein enhancer formation and mediates transcription activation by GABP. EMBO J. 2000 Feb 15;19(4):683-90. PMID:10675337 doi:10.1093/emboj/19.4.683
- ↑ Mahajan SS, Wilson AC. Mutations in host cell factor 1 separate its role in cell proliferation from recruitment of VP16 and LZIP. Mol Cell Biol. 2000 Feb;20(3):919-28. PMID:10629049
- ↑ Scarr RB, Smith MR, Beddall M, Sharp PA. A novel 50-kilodalton fragment of host cell factor 1 (C1) in G(0) cells. Mol Cell Biol. 2000 May;20(10):3568-75. PMID:10779346
- ↑ Piluso D, Bilan P, Capone JP. Host cell factor-1 interacts with and antagonizes transactivation by the cell cycle regulatory factor Miz-1. J Biol Chem. 2002 Nov 29;277(48):46799-808. Epub 2002 Sep 19. PMID:12244100 doi:10.1074/jbc.M206226200
- ↑ Luciano RL, Wilson AC. HCF-1 functions as a coactivator for the zinc finger protein Krox20. J Biol Chem. 2003 Dec 19;278(51):51116-24. Epub 2003 Oct 6. PMID:14532282 doi:10.1074/jbc.M303470200
- ↑ 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 Dev. 2003 Apr 1;17(7):896-911. PMID:12670868 doi:10.1101/gad.252103
- ↑ Khurana B, Kristie TM. A protein sequestering system reveals control of cellular programs by the transcriptional coactivator HCF-1. J Biol Chem. 2004 Aug 6;279(32):33673-83. Epub 2004 Jun 8. PMID:15190068 doi:10.1074/jbc.M401255200
- ↑ Vogel JL, Kristie TM. Site-specific proteolysis of the transcriptional coactivator HCF-1 can regulate its interaction with protein cofactors. Proc Natl Acad Sci U S A. 2006 May 2;103(18):6817-22. Epub 2006 Apr 19. PMID:16624878 doi:0602109103
- ↑ Narayanan A, Ruyechan WT, Kristie TM. 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 Jun 26;104(26):10835-40. Epub 2007 Jun 19. PMID:17578910 doi:10.1073/pnas.0704351104
- ↑ Cai Y, Jin J, Swanson SK, Cole MD, Choi SH, Florens L, Washburn MP, Conaway JW, Conaway RC. Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex. J Biol Chem. 2010 Feb 12;285(7):4268-72. doi: 10.1074/jbc.C109.087981. Epub 2009 , Dec 14. PMID:20018852 doi:10.1074/jbc.C109.087981
- ↑ Mazars R, Gonzalez-de-Peredo A, Cayrol C, Lavigne AC, Vogel JL, Ortega N, Lacroix C, Gautier V, Huet G, Ray A, Monsarrat B, Kristie TM, Girard JP. 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 Apr 30;285(18):13364-71. doi: 10.1074/jbc.M109.072579. Epub, 2010 Mar 3. PMID:20200153 doi:10.1074/jbc.M109.072579
- ↑ Park J, Lammers F, Herr W, Song JJ. HCF-1 self-association via an interdigitated Fn3 structure facilitates transcriptional regulatory complex formation. Proc Natl Acad Sci U S A. 2012 Oct 8. PMID:23045687 doi:10.1073/pnas.1208378109
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