Retinoic acid modulates the retinoblastoma protein during adipocyte terminal differentiation.
Terminal differentiation is characterized by a permanent withdrawal of cells from the cell cycle. Retinoblastoma protein (RB) has been involved in cell cycle progression. Accumulating evidence also implicates RB in the promotion of differentiation of many cell types. We present new insights into the role of RB and other cell cycle regulatory proteins in adipocyte differentiation and on the role of retinoic acid (RA) in the regulation of the latter process. It is shown that RA reduces RB expression and enhances RB phosphorylation by a mechanism that involves down-regulation of the cyclin-dependent kinase inhibitor (CKI) p21(Cip1), having this fact as important consequences for both the cell cycle progression and the adipocyte differentiation process. The effects of RA result in the blockage of adipogenesis, but may also favor the retention of a pool of adipose cells able to re-enter the cell cycle, which may be important for the developmental dynamics of adipose tissue in vivo. In addition, these results reinforce the idea that there is a cross-talk between the cell cycle machinery and the adipocyte differentiation machinery that can be modulated by external signals, including nutrients.
Ribot
Joan
J
Fundamental Biology and Health Sciences, University of the Balearic Islands (UIB), Cra. Valldemossa, km 7.5, 07122 Palma de Mallorca, Illes Balears, Spain.
Oliver
Paula
P
Serra
Francisca
F
Palou
Andreu
A
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D006224:Cricetinae; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D016160:Retinoblastoma Protein; D014212:Tretinoin