Hypermethylated in cancer 1 protein

Definition:

Transcriptional repressor. Recognizes and binds to the consensus sequence '5-[CG]NG[CG]GGGCA[CA]CC-3'. May act as a tumor suppressor. Involved in development of head, face, limbs and ventral body wall (By similarity). Involved in down-regulation of SIRT1 and thereby is involved in regulation of p53/TP53-dependent apoptotic DNA-damage responses. The specific target gene promoter association seems to be depend on corepressors, such as CTBP1 or CTBP2 and MTA1. In cooperation with MTA1 (indicative for an association with the NuRD complex) represses transcription from CCND1/cyclin-D1 and CDKN1C/p57Kip2 specifically in quiescent cells. Involved in regulation of the Wnt signaling pathway probably by association with TCF7L2 and preventing TCF7L2 and CTNNB1 association with promoters of TCF-responsive genes. Seems to repress transcription from E2F1 and ATOH1 which involves ARID1A, indicative for the participation of a distinct SWI/SNF-type chromatin-remodeling complex. Probably represses transcription of ACKR3, FGFBP1 and EFNA1.

References:

[1]. Sébastien Pinte, et al. The tumor suppressor gene HIC1 (hypermethylated in cancer 1) is a sequence-specific transcriptional repressor: definition of its consensus binding sequence and analysis of its DNA binding and repressive properties. J Biol Chem. 2004 Sep 10;279(37):38313-24. [Content Brief]

[2]. Kimberly J Briggs, et al. Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma. Genes Dev. 2008 Mar 15;22(6):770-85. [Content Brief]

[3]. Wen Yong Chen, et al. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell. 2005 Nov 4;123(3):437-48. [Content Brief]

[4]. Tomas Valenta, et al. HIC1 attenuates Wnt signaling by recruitment of TCF-4 and beta-catenin to the nuclear bodies. EMBO J. 2006 Jun 7;25(11):2326-37. [Content Brief]

[5]. Capucine Van Rechem, et al. HIC1 interacts with a specific subunit of SWI/SNF complexes, ARID1A/BAF250A. Biochem Biophys Res Commun. 2009 Aug 7;385(4):586-90. [Content Brief]

[6]. Sophie Deltour, et al. The human candidate tumor suppressor gene HIC1 recruits CtBP through a degenerate GLDLSKK motif. Mol Cell Biol. 2002 Jul;22(13):4890-901. [Content Brief]

[7]. W Zhang, et al. A potential tumor suppressor role for Hic1 in breast cancer through transcriptional repression of ephrin-A1. Oncogene. 2010 Apr 29;29(17):2467-76. [Content Brief]

[8]. Victorino R Briones, et al. Mechanism of fibroblast growth factor-binding protein 1 repression by TGF-beta. Biochem Biophys Res Commun. 2006 Jun 30;345(2):595-601. [Content Brief]

[9]. Capucine Van Rechem, et al. Scavenger chemokine (CXC motif) receptor 7 (CXCR7) is a direct target gene of HIC1 (hypermethylated in cancer 1). J Biol Chem. 2009 Jul 31;284(31):20927-35. [Content Brief]

[10]. Capucine Van Rechem, et al. Differential regulation of HIC1 target genes by CtBP and NuRD, via an acetylation/SUMOylation switch, in quiescent versus proliferating cells. Mol Cell Biol. 2010 Aug;30(16):4045-59. [Content Brief]

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