title: Cdk4 promotes adipogenesis through PPARgamma activation.
abstract: Cell cycle regulators such as E2F1 and retinoblastoma (RB) play crucial roles in the control of adipogenesis, mostly by controlling the transition between preadipocyte proliferation and adipocyte differentiation. The serine-threonine kinase cyclin-dependent kinase 4 (cdk4) works in a complex with D-type cyclins to phosphorylate RB, mediating the entry of cells into the cell cycle in response to external stimuli. Because cdk4 is an upstream regulator of the E2F-RB pathway, we tested whether cdk4 was a target for new factors that regulate adipogenesis. Here we find that cdk4 inhibition impairs adipocyte differentiation and function. Disruption of cdk4 or activating mutations in cdk4 in primary mouse embryonic fibroblasts results in reduced and increased adipogenic potential, respectively, of these cells. We show that the effects of cdk4 are not limited to the control of differentiation; cdk4 also participates in adipocyte function through activation of PPARgamma.
authors.affiliation: Inserm U540, Equipe Avenir, F-34090 Montpellier, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Abella
authors.forename: Pierre
authors.initials: P
authors.lastname: Dubus
authors.forename: Marcos
authors.initials: M
authors.lastname: Malumbres
authors.forename: Sushil G
authors.initials: SG
authors.lastname: Rane
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kiyokawa
authors.forename: Audrey
authors.initials: A
authors.lastname: Sicard
authors.forename: Françoise
authors.initials: F
authors.lastname: Vignon
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.forename: Mariano
authors.initials: M
authors.lastname: Barbacid
authors.forename: Lluis
authors.initials: L
authors.lastname: Fajas
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001692:Biological Transport; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D047495:PPAR gamma; D012333:RNA, Messenger; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D005947:Glucose