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PMID: 11331609 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Sharp, an inducible cofactor that integrates nuclear receptor repression and activation.

Genes & development ·Vol. 15 ·No. 9 ·2001-05-01 ·Pages 1140-51

Shi Y, Downes M, Xie W, Kao HY, Ordentlich P, Tsai CC, Hon M, Evans RM

Abstract

A yeast two-hybrid screen using the conserved carboxyl terminus of the nuclear receptor corepressor SMRT as a bait led to the isolation of a novel human gene termed SHARP (SMRT/HDAC1 Associated Repressor Protein). SHARP is a potent transcriptional repressor whose repression domain (RD) interacts directly with SMRT and at least five members of the NuRD complex including HDAC1 and HDAC2. In addition, SHARP binds to the steroid receptor RNA coactivator SRA via an intrinsic RNA binding domain and suppresses SRA-potentiated steroid receptor transcription activity. Accordingly, SHARP has the capacity to modulate both liganded and nonliganded nuclear receptors. Surprisingly, the expression of SHARP is itself steroid inducible, suggesting a simple feedback mechanism for attenuation of the hormonal response.

MeSH Terms
Amino Acid Motifs Amino Acid Sequence Animals Base Sequence Cloning, Molecular Conserved Sequence DNA-Binding Proteins/genetics,metabolism Estrogens/metabolism Histone Deacetylase 1 Histone Deacetylase 2 Histone Deacetylases/genetics,metabolism Humans Mice Molecular Sequence Data Nuclear Receptor Co-Repressor 2 RNA, Long Noncoding RNA, Untranslated Receptors, Cytoplasmic and Nuclear/metabolism Receptors, Estrogen/metabolism Repressor Proteins/genetics,metabolism
Chemicals
DNA-Binding Proteins Estrogens NCOR2 protein, human Ncor2 protein, mouse Nuclear Receptor Co-Repressor 2 RNA, Long Noncoding RNA, Untranslated Receptors, Cytoplasmic and Nuclear Receptors, Estrogen Repressor Proteins steroid receptor RNA activator HDAC1 protein, human Hdac2 protein, mouse Histone Deacetylase 1 Histone Deacetylase 2 Histone Deacetylases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Shi Y
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
Downes M
Xie W
Kao H Y
Ordentlich P
Tsai C C
Hon M
Evans R M
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.871201
Published
2001-05-01
Pages
1140-51
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC312688
Subset
IM
Grants
NICHD NIH HHS · R01 HD027183 · United States
NIDDK NIH HHS · R37 DK057978 · United States
NIDDK NIH HHS · 9R01DK57978 · United States
NICHD NIH HHS · HD27183 · United States
External Links
PubMed source DOI: 10.1101/gad.871201 PMC Full Text View journal details
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