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PMID: 12110588 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Phosphorylation by p38MAPK and recruitment of SUG-1 are required for RA-induced RAR gamma degradation and transactivation.

The EMBO journal ·Vol. 21 ·No. 14 ·2002-07-15 ·Pages 3760-9

Giannì M, Bauer A, Garattini E, Chambon P, Rochette-Egly C

Abstract

The nuclear retinoic acid receptor RAR gamma 2 undergoes proteasome-dependent degradation upon ligand binding. Here we provide evidence that the domains that signal proteasome-mediated degradation overlap with those that activate transcription, i.e. the activation domains AF-1 and AF-2. The AF-1 domain signals RAR gamma 2 degradation through its phosphorylation by p38MAPK in response to RA. The AF-2 domain acts via the recruitment of SUG-1, which belongs to the 19S regulatory subunit of the 26S proteasome. Blocking RAR gamma 2 degradation through inhibition of either the p38MAPK pathway or the 26S proteasome function impairs its RA-induced transactivation activity. Thus, the turnover of RAR gamma 2 is linked to transactivation.

MeSH Terms
ATPases Associated with Diverse Cellular Activities Adaptor Proteins, Signal Transducing Animals COS Cells Carrier Proteins/metabolism Cysteine Endopeptidases/metabolism Intracellular Signaling Peptides and Proteins LIM Domain Proteins Ligands Mitogen-Activated Protein Kinases/metabolism Multienzyme Complexes/metabolism Phosphorylation Proteasome Endopeptidase Complex Receptors, Retinoic Acid/genetics,metabolism Transcription Factors Transcriptional Activation/drug effects Tretinoin/pharmacology Ubiquitin/metabolism p38 Mitogen-Activated Protein Kinases
Chemicals
Adaptor Proteins, Signal Transducing Carrier Proteins Intracellular Signaling Peptides and Proteins LIM Domain Proteins Ligands Multienzyme Complexes PSMC5 protein, human Receptors, Retinoic Acid SUG1 protein, mammalian Transcription Factors Ubiquitin retinoic acid receptor gamma Tretinoin Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases Cysteine Endopeptidases Proteasome Endopeptidase Complex ATPases Associated with Diverse Cellular Activities
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Giannì Maurizio
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, BP 163, 67404 Illkirch cedex, France.
Bauer Annie
Garattini Enrico
Chambon Pierre
Rochette-Egly Cécile
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdf374
Published
2002-07-15
Pages
3760-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC126119
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdf374 PMC Full Text View journal details
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