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PPARgamma induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A

, : PPARgamma induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes & Development 11(15): 1987-1998

PPAR-gamma is an adipose-selective nuclear hormone receptor that plays a key role in the control of adipocyte differentiation. Previous studies indicated that activation of ectopically expressed PPAR-gamma induces differentiation when cells have ceased growth because of confluence. We show here that ligand activation of PPAR-gamma is sufficient to induce growth arrest in fibroblasts and SV40 large T-antigen transformed, adipogenic HIB1B cells. Cell cycle withdrawal is accompanied by a decrease in the DNA-binding and transcriptional activity of the E2F/DP complex, which is attributable to an increase in the phosphorylation of these proteins, especially DP-1. This effect is a consequence of decreased expression of the catalytic subunit of the serine-threonine phosphatase PP2A. These data suggest an important role for PP2A in the control of E2F/DP activity and a new mode of cell cycle control in differentiation.


PMID: 9271121

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