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PMID: 10077563 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Unique forms of human and mouse nuclear receptor corepressor SMRT.

Ordentlich P, Downes M, Xie W, Genin A, Spinner NB, Evans RM

Abstract

Nuclear hormone receptors have been shown to repress transcription in the absence of ligand. This repression is mediated by a corepressor complex that contains the Sin3A protein and histone deacetylases (HDAC1 and 2). Studies by several groups demonstrate that this complex is recruited to nuclear receptors through the highly related corepressors SMRT (silencing mediator of retinoid acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor). We describe here the cloning, characterization, and chromosomal mapping of forms of human and mouse SMRT that includes a 1,000-aa extension, which reveals striking homology to the amino terminus of N-CoR. Structure and function studies of wild-type and natural splicing variants suggest the presence of 3-4 amino terminal domains that repress in a cooperative as well as mechanistically distinct fashion.

MeSH Terms
Amino Acid Sequence Animals Chromosome Mapping Chromosomes, Human, Pair 12 Cloning, Molecular DNA, Complementary/analysis,genetics DNA-Binding Proteins/genetics Humans Mice Molecular Sequence Data Nuclear Receptor Co-Repressor 2 Receptors, Cytoplasmic and Nuclear/genetics Repressor Proteins/genetics Sequence Alignment Sequence Analysis
Chemicals
DNA, Complementary DNA-Binding Proteins NCOR2 protein, human Ncor2 protein, mouse Nuclear Receptor Co-Repressor 2 Receptors, Cytoplasmic and Nuclear Repressor Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ordentlich P
Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Downes M
Xie W
Genin A
Spinner N B
Evans R M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1999-03-16
Pages
2639-44
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC15821
Subset
IM
Databases
GENBANK
AF113001, AF113002, AF113003
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