Two receptor interaction domains in the corepressor, N-CoR/RIP13, are required for an efficient interaction with Rev-erbAα and RVR: Physical association is dependent on the E region of the orphan receptors

Downes M., Burke L.J., Bailey P.J. and Muscat G.E.O. (1996) Two receptor interaction domains in the corepressor, N-CoR/RIP13, are required for an efficient interaction with Rev-erbAα and RVR: Physical association is dependent on the E region of the orphan receptors. Nucleic Acids Research, 24 22: 4379-4386. doi:10.1093/nar/24.22.4379


Author Downes M.
Burke L.J.
Bailey P.J.
Muscat G.E.O.
Title Two receptor interaction domains in the corepressor, N-CoR/RIP13, are required for an efficient interaction with Rev-erbAα and RVR: Physical association is dependent on the E region of the orphan receptors
Journal name Nucleic Acids Research   Check publisher's open access policy
ISSN 0305-1048
Publication date 1996-01-01
Year available 1996
Sub-type Article (original research)
DOI 10.1093/nar/24.22.4379
Open Access Status DOI
Volume 24
Issue 22
Start page 4379
End page 4386
Total pages 8
Place of publication OXFORD
Publisher OXFORD UNIV PRESS UNITED KINGDOM
Language eng
Subject 1311 Genetics
Abstract Rev-erbA alpha and RVR/Rev-erb beta/BD73 are orphan steroid receptors that have no known ligands in the 'classical sense', These 'orphans' do not activate transcription, but function as dominant transcriptional silencers, The thyroid hormone receptor (TR) and the retinoic acid receptor (RAR) act as transcriptional silencers by binding corepressors (e.g. N-CoR/RIP13 and SMRT/TRAC-2) in the absence of ligands, The molecular basis of repression by orphan receptors, however, remains obscure, and it is unclear whether these corepressors mediate transcriptional silencing by Rev-erbA alpha and RVR, Recently, two new variants of N-CoR have been described, RIP13a and RIP13 Delta 1. The characterisation of these splice variants has identified a second receptor interaction domain (ID-II), in addition to the previously characterised interaction domain (ID-I), This investigation utilised the mammalian two hybrid system and transfection analysis to demonstrate that Rev-erbA alpha and RVR will not efficiently interact with either ID-I or ID-II separately from RIP13a or RIP13 Delta 1. However, they interact efficiently with a domain composed of ID-I and ID-II from RIP13a, Interestingly, the interaction of Rev-erbA alpha and RVR is strongest with ID-I and ID-II from RIP13 Delta 1. Detailed deletion analysis of the orphan receptor interaction with RIP13/N-CoR rigorously demonstrated that the physical association was critically dependent on an intact E region of Rev-erbA alpha and RVR, Over-expression of the corepressor interaction domains (i.e. dominant negative forms of N-CoR/RIP13) could alleviate orphan receptor-mediated repression of transactivation by GALVP16, This demonstrated that these regions could function as anti-repressors. In conclusion, these data from two independent approaches demonstrate that repression by Rev-erbA alpha and RVR is mediated by an interaction of ID-I and ID-II of N-CoR, RIP13a and Delta 1 with the putative ligand binding domain of the orphan receptors.
Keyword Thyroid-Hormone-Receptor
Retinoid-X Receptor
Nuclear Receptor
Response Element
Co-Repressor
Activates Transcription
Opposite Strand
Binding-Site
Superfamily
Gene
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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Citation counts: TR Web of Science Citation Count  Cited 74 times in Thomson Reuters Web of Science Article | Citations
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