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:
↑Wilson AC, LaMarco K, Peterson MG, Herr W (Jul 1993). "The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein". Cell. 74 (1): 115–25. doi:10.1016/0092-8674(93)90299-6. PMID8392914.
↑Kristie TM, Sharp PA (Mar 1993). "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. PMID8454622.
↑Gunther M, Laithier M, Brison O (Jul 2000). "A set of proteins interacting with transcription factor Sp1 identified in a two-hybrid screening". Molecular and Cellular Biochemistry. 210 (1–2): 131–42. doi:10.1023/A:1007177623283. PMID10976766.
↑Piluso D, Bilan P, Capone JP (Nov 2002). "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. doi:10.1074/jbc.M206226200. PMID12244100.
Wilson AC, Peterson MG, Herr W (Oct 1995). "The HCF repeat is an unusual proteolytic cleavage signal". Genes & Development. 9 (20): 2445–58. doi:10.1101/gad.9.20.2445. PMID7590226.
Frattini A, Faranda S, Redolfi E, Zucchi I, Villa A, Patrosso MC, Strina D, Susani L, Vezzoni P (Sep 1994). "Genomic organization of the human VP16 accessory protein, a housekeeping gene (HCFC1) mapping to Xq28". Genomics. 23 (1): 30–5. doi:10.1006/geno.1994.1455. PMID7829097.
Kristie TM, Pomerantz JL, Twomey TC, Parent SA, Sharp PA (Mar 1995). "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. doi:10.1074/jbc.270.9.4387. PMID7876203.
Kristie TM, Sharp PA (Mar 1993). "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. PMID8454622.
Zoppè M, Frattini A, Faranda S, Vezzoni P (May 1996). "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. doi:10.1006/geno.1996.0244. PMID8661027.
Choi Y, Asada S, Uesugi M (May 2000). "Divergent hTAFII31-binding motifs hidden in activation domains". The Journal of Biological Chemistry. 275 (21): 15912–6. doi:10.1074/jbc.275.21.15912. PMID10821850.