Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis.

Détails

ID Serval
serval:BIB_B5554A508C70
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis.
Périodique
Molecular Endocrinology
Auteur(s)
Iankova I., Petersen R.K., Annicotte J.S., Chavey C., Hansen J.B., Kratchmarova I., Sarruf D., Benkirane M., Kristiansen K., Fajas L.
ISSN
0888-8809 (Print)
ISSN-L
0888-8809
Statut éditorial
Publié
Date de publication
2006
Volume
20
Numéro
7
Pages
1494-1505
Langue
anglais
Résumé
Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9 in adipogenesis. In this study we show that the expression of the cdk9 p55 isoform is highly regulated during 3T3-L1 adipocyte differentiation at RNA and protein levels. Furthermore, cdk9, as well as cyclin T1 and cyclin T2, shows differences in nuclear localization at distinct stages of adipogenesis. Overexpression of cdk9 increases the adipogenic potential of 3T3-L1 cells, whereas inhibition of cdk9 by specific cdk inhibitors, and dominant-negative cdk9 mutant impairs adipogenesis. We show that the positive effects of cdk9 on the differentiation of 3T3-L1 cells are mediated by a direct interaction with and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master regulator of this process, on the promoter of PPARgamma target genes. PPARgamma-cdk9 interaction results in increased transcriptional activity of PPARgamma and therefore increased adipogenesis.
Mots-clé
3T3 Cells, Adipogenesis/drug effects, Adipogenesis/physiology, Animals, CHO Cells, Cell Differentiation, Cell Division/drug effects, Cricetinae, Cyclin-Dependent Kinase 9/antagonists & inhibitors, Cyclin-Dependent Kinase 9/metabolism, Dichlororibofuranosylbenzimidazole/pharmacology, Gene Expression Regulation, Mice, PPAR gamma/metabolism, Phosphorylation, Positive Transcriptional Elongation Factor B/metabolism, Protein Binding
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/03/2013 16:02
Dernière modification de la notice
20/08/2019 15:23
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