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RIF‐1, a novel nuclear receptor corepressor that associates with the nuclear matrix
Author(s) -
Li Hui Joyce,
Haque Zaffar K.,
Chen Amy,
Mendelsohn Michael
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21340
Subject(s) - corepressor , nuclear matrix , transcription factor , nuclear localization sequence , biology , nuclear receptor , nuclear protein , microbiology and biotechnology , repressor , psychological repression , nuclear receptor co repressor 1 , cytoplasm , genetics , gene expression , chromatin , gene
The retinoic acid receptors (RARs) are ligand‐dependent transcription factors that play critical roles in cell differentiation, embryonic development, and tumor suppression. RAR transcriptional activities are mediated by a growing family of nuclear receptor (NR) coregulators. Here we report the cloning and characterization of a novel protein RIF1 (receptor interacting factor) that interacts with RARα in vivo and in vitro. RIF1 encodes a novel 739 amino acid protein that is ubiquitously expressed in a variety of tissues and cell lines. GST‐pull down assays show that RIF1 also interacts with a number of other NRs. The interaction domain of RIF1 for RARα is located at the C‐terminal region of RIF1, between amino acids 512 and 674. RIF1 is localized exclusively in the cell nucleus and specifically to the nuclear matrix. Mutation of the nuclear localization signal abolishes this nuclear localization and causes RIF1 to appear in the cytoplasm. Co‐transfection of RIF1 with RAR causes RAR to localize to the nuclear matrix. RIF1 contains a strong transcriptional repression domain that robustly inhibits ligand‐dependent transcriptional activation by RARα. This domain is located to the distal C‐terminal 100 amino acids, distinct from the RARα‐interaction and nuclear matrix‐targeting domains. The transcriptional repression activity of RIF1 is mediated at least in part through direct recruitment of histone deacetylases. This study identifies RIF1 as a novel nuclear matrix transcription repressor, and suggests a potential role of RIF1 that regulates NR transcriptional activity. J. Cell. Biochem. 102: 1021–1035, 2007. © 2007 Wiley‐Liss, Inc.