¹Institut de Génétique et de Biologie Moléculaire et Cellulaire/CNRS/INSERM/ULP, 67404 Illkirch, France

Correspondence: J Auwerx, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries, 67404 Illkirch, France. E-mail: auwerx@igbmc.u-strasbg.fr

Received 20 September 2002; Revised 21 February 2003; Accepted 24 February 2003.

Abstract

The nuclear receptor PPAR is implicated in the control of cell proliferation and apoptosis. However, the molecular mechanisms by which it controls these processes remain largely elusive. We show here that PPAR activation in the presence of the retinoblastoma protein (RB) results in the arrest of cells at the G1 phase of the cell cycle, whereas in the absence of RB, cells accumulate in G2/M, endoreduplicate, and undergo apoptosis. Through the use of HDAC inhibitors and coimmunoprecipitations, we furthermore demonstrate that the effects of RB on PPAR-mediated control of the cell cycle and apoptosis depend on the recruitment of histone deacetylase 3 (HDAC3) to PPAR. In combination, these data hence demonstrate that the effects of PPAR on cell proliferation and apoptosis are dependent on the presence of an RB–HDAC3 complex.