Activation of Peroxisome Proliferator-activated Receptor γ Bypasses the Function of the Retinoblastoma Protein in Adipocyte Differentiation

Jacob B. Hansen, Rasmus K. Petersen, Berit M. Larsen, Jirina Bartkova, Jan Alsner, Karsten Kristiansen
1999 Journal of Biological Chemistry  
The retinoblastoma protein (pRB) is an important regulator of development, proliferation, and cellular differentiation. pRB was recently shown to play a pivotal role in adipocyte differentiation, to interact physically with adipogenic CCAAT/enhancer-binding proteins (C/ EBPs), and to positively regulate transactivation by C/EBP␤. We show that PPAR␥-mediated transactivation is pRB-independent, and that ligand-induced transactivation by PPAR␥1 present in RB ؉/؉ and RB ؊/؊ mouse embryo fibroblasts
more » ... is sufficient to bypass the differentiation block imposed by the absence of pRB. The differentiated RB ؊/؊ cells accumulate lipid and express adipocyte markers, including C/EBP␣ and PPAR␥2. Interestingly, adipose conversion of pRB-deficient cells occurs in the absence of compensatory up-regulations of the other pRB family members p107 and p130. RB ؉/؉ as well as RB ؊/؊ cells efficiently exit from the cell cycle after completion of clonal expansion following stimulation with adipogenic inducers. We conclude that ligandinduced activation of endogenous PPAR␥1 in mouse embryo fibroblasts is sufficient to initiate a transcriptional cascade resulting in induction of PPAR␥2 and C/EBP␣ expression, withdrawal from the cell cycle, and terminal differentiation in the absence of a functional pRB.
doi:10.1074/jbc.274.4.2386 pmid:9891007 fatcat:fovqki4wqrf73frwh5k5beqiwm