PPARgamma Recruits the P-TEFb Complex to Activate Transcription and Promote Adipogenesis. Export

@article{citeulike:532045, abstract = {Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II (RNA pol II), facilitating transcriptional elongation. Beside 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). Since 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, show 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 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.}, address = {Inserm, U540, Equipe Avenir, Montpellier, F-34090, France; Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark; Institut de G\'{e}netique Humaine, F-34090 Montpellier, France; Centre Hospitalier Universitaire Arnaud de Villeneuve, Montpellier, F-34090, France.}, author = {Iankova, Irena and Petersen, Rasmus K K. and Annicotte, Jean-S\'{e}bastien S. and Chavey, Carine and Hansen, Jacob B B. and Kratchmarova, Irina and Sarruf, David and Benkirane, Monsef and Kristiansen, Karsten and Fajas, Lluis}, citeulike-article-id = {532045}, citeulike-linkout-0 = {http://dx.doi.org/10.1210/me.2005-0222}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16484339}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16484339}, day = {16}, doi = {10.1210/me.2005-0222}, issn = {0888-8809}, journal = {Mol Endocrinol}, keywords = {adipogenesis, cdk9, cyclint, drb, elongation, nuclear, p-tefb, ppar, receptor, transcription}, month = {February}, posted-at = {2006-03-06 23:34:15}, priority = {2}, title = {PPAR{gamma} Recruits the P-TEFb Complex to Activate Transcription and Promote Adipogenesis.}, url = {http://dx.doi.org/10.1210/me.2005-0222}, year = {2006} }

TY - JOUR ID - citeulike:532045 L3 - citeulike-article-id:532045 N2 - Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II (RNA pol II), facilitating transcriptional elongation. Beside 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). Since 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, show 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 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. JF - Mol Endocrinol SN - 0888-8809 AD - Inserm, U540, Equipe Avenir, Montpellier, F-34090, France; Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark; Institut de Génetique Humaine, F-34090 Montpellier, France; Centre Hospitalier Universitaire Arnaud de Villeneuve, Montpellier, F-34090, France. TI - PPAR{gamma} Recruits the P-TEFb Complex to Activate Transcription and Promote Adipogenesis. KW - adipogenesis KW - cdk9 KW - cyclint KW - drb KW - elongation KW - nuclear KW - p-tefb KW - ppar KW - receptor KW - transcription AU - Iankova, Irena AU - Petersen, Rasmus K AU - Annicotte, Jean-Sébastien AU - Chavey, Carine AU - Hansen, Jacob B AU - Kratchmarova, Irina AU - Sarruf, David AU - Benkirane, Monsef AU - Kristiansen, Karsten AU - Fajas, Lluis PY - 2006/02/16/ UR - http://dx.doi.org/10.1210/me.2005-0222 ER -