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

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... 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.