Cdk4 promotes adipogenesis through PPARgamma activation.
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.
Abella
Anna
A
Inserm U540, Equipe Avenir, F-34090 Montpellier, France.
Dubus
Pierre
P
Malumbres
Marcos
M
Rane
Sushil G
SG
Kiyokawa
Hiroaki
H
Sicard
Audrey
A
Vignon
Françoise
F
Langin
Dominique
D
Barbacid
Mariano
M
Fajas
Lluis
L
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
D047495:PPAR gamma; D012333:RNA, Messenger; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D005947:Glucose