Modulation of lysine acetylation-stimulated repressive activity by Erk2-mediated phosphorylation of RIP140 in adipocyte differentiation.

Détails

ID Serval
serval:BIB_09813B29D7AF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Modulation of lysine acetylation-stimulated repressive activity by Erk2-mediated phosphorylation of RIP140 in adipocyte differentiation.
Périodique
Cellular signalling
Auteur(s)
Ho P.C., Gupta P., Tsui Y.C., Ha S.G., Huq M., Wei L.N.
ISSN
0898-6568 (Print)
ISSN-L
0898-6568
Statut éditorial
Publié
Date de publication
10/2008
Peer-reviewed
Oui
Volume
20
Numéro
10
Pages
1911-1919
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Receptor-interacting protein 140 is a co-regulator for many transcription factors. Previous mass spectrometry studies showed that either phosphorylation or lysine acetylation of RIP140 directly enhanced its trans-repressive activity. In this study, we first identified p300 as a specific lysine acetyltransferase, and extracellular-signal-related kinase 2 (Erk2) as a specific kinase for threonine phosphorylation, of RIP140 in vivo. We further determined two specific acetylated lysine residues (Lys(158)/Lys(287)) and phosphorylated threonine residues (Thr(202)/Thr(207)) that were critical for its gene-repressive activity. We then delineated signal transduction from Erk2-mediated phosphorylation of RIP140 that enhanced its recruiting p300 for subsequent lysine acetylation, and demonstrated the kinetics of activation of this signal transduction pathway in differentiating adipocytes. Finally, the physiological significance of this cell signal transduction pathway was illustrated in rescuing experiments where the defect in fat accumulation of RIP140-null cultures was rescued by re-expressing the wild type RIP140 or its phospho-mimetic mutant, but not its acetylation deficient mutant. These results demonstrate the signal transduction pathway, initiated from Erk2 activation for specific threonine phosphorylation, followed by p300 recruitment for lysine acetylation, which ultimately enhances the gene-repressive activity of RIP140 and its functional role in fat accumulation in differentiated adipocytes.
Mots-clé
3T3-L1 Cells, Acetylation, Adaptor Proteins, Signal Transducing/metabolism, Adipocytes/cytology, Adipocytes/enzymology, Animals, COS Cells, Cell Differentiation, Cercopithecus aethiops, Enzyme Activation, Kinetics, Lipid Metabolism, Lysine/metabolism, Mice, Mitogen-Activated Protein Kinase 1/metabolism, Nuclear Proteins/metabolism, Nuclear Receptor Interacting Protein 1, Phosphorylation, Phosphothreonine/metabolism, Protein Binding, Repressor Proteins/metabolism, p300-CBP Transcription Factors/metabolism
Pubmed
Web of science
Création de la notice
05/04/2019 15:42
Dernière modification de la notice
20/08/2019 12:31
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