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Transcription intermediary factor 1-beta

Definition:

Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions.; (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1.

References:

[1]. Chuangui Wang, et al. Regulation of E2F1 function by the nuclear corepressor KAP1. J Biol Chem. 2007 Oct 12;282(41):29902-9. [Content Brief]

[2]. Jennifer M Doyle, et al. MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases. Mol Cell. 2010 Sep 24;39(6):963-74. [Content Brief]

[3]. J R Friedman, et al. KAP-1, a novel corepressor for the highly conserved KRAB repression domain. Genes Dev. 1996 Aug 15;10(16):2067-78. [Content Brief]

[4]. Chuangui Wang, et al. MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation. EMBO J. 2005 Sep 21;24(18):3279-90. [Content Brief]

[5]. Ryan W Serra, et al. A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype. Elife. 2014 Mar 12;3:e02313. [Content Brief]

[6]. Maureen Gilmore-Hebert, et al. Interactions of ErbB4 and Kap1 connect the growth factor and DNA damage response pathways. Mol Cancer Res. 2010 Oct;8(10):1388-98. [Content Brief]

[7]. Xu Li, et al. SUMOylation of the transcriptional co-repressor KAP1 is regulated by the serine and threonine phosphatase PP1. Sci Signal. 2010 Apr 27;3(119):ra32. [Content Brief]

[8]. Chikage Suzuki, et al. A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor associated with KAP-1. Biochem Biophys Res Commun. 2008 Feb 1;366(1):226-32. [Content Brief]

[9]. Yael Ziv, et al. Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway. Nat Cell Biol. 2006 Aug;8(8):870-6. [Content Brief]

[10]. Rui Sun, et al. Kaposi's sarcoma-associated herpesvirus-encoded LANA interacts with host KAP1 to facilitate establishment of viral latency. J Virol. 2014 Jul;88(13):7331-44. [Content Brief]

[11]. David E White, et al. KAP1, a novel substrate for PIKK family members, colocalizes with numerous damage response factors at DNA lesions. Cancer Res. 2006 Dec 15;66(24):11594-9. [Content Brief]

[12]. David Valle-García, et al. ATRX binds to atypical chromatin domains at the 3' exons of zinc finger genes to preserve H3K9me3 enrichment. Epigenetics. 2016 Jun 2;11(6):398-414. [Content Brief]

[13]. P Moosmann, et al. Transcriptional repression by RING finger protein TIF1 beta that interacts with the KRAB repressor domain of KOX1. Nucleic Acids Res. 1996 Dec 15;24(24):4859-67. [Content Brief]

[14]. Alexey V Ivanov, et al. PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing. Mol Cell. 2007 Dec 14;28(5):823-37. [Content Brief]

[15]. Xu Li, et al. Role for KAP1 serine 824 phosphorylation and sumoylation/desumoylation switch in regulating KAP1-mediated transcriptional repression. J Biol Chem. 2007 Dec 14;282(50):36177-89. [Content Brief]

[16]. Chunjian Huang, et al. Cutting Edge: a novel, human-specific interacting protein couples FOXP3 to a chromatin-remodeling complex that contains KAP1/TRIM28. J Immunol. 2013 May 1;190(9):4470-3. [Content Brief]

[17]. Qiming Liang, et al. Tripartite motif-containing protein 28 is a small ubiquitin-related modifier E3 ligase and negative regulator of IFN regulatory factor 7. J Immunol. 2011 Nov 1;187(9):4754-63. [Content Brief]

[18]. Wei Wang, et al. Novel activity of KRAB domain that functions to reinforce nuclear localization of KRAB-containing zinc finger proteins by interacting with KAP1. Cell Mol Life Sci. 2013 Oct;70(20):3947-58. [Content Brief]

[19]. Mark S Lechner, et al. The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain. Biochem Biophys Res Commun. 2005 Jun 17;331(4):929-37. [Content Brief]

[20]. David C Schultz, et al. SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev. 2002 Apr 15;16(8):919-32. [Content Brief]

[21]. Y Agata, et al. Two novel Krüppel-associated box-containing zinc-finger proteins, KRAZ1 and KRAZ2, repress transcription through functional interaction with the corepressor KAP-1 (TIF1beta/KRIP-1). J Biol Chem. 1999 Jun 4;274(23):16412-22. [Content Brief]

[22]. Yung-Kang Lee, et al. Doxorubicin down-regulates Kruppel-associated box domain-associated protein 1 sumoylation that relieves its transcription repression on p21WAF1/CIP1 in breast cancer MCF-7 cells. J Biol Chem. 2007 Jan 19;282(3):1595-606. [Content Brief]

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