Abstract
The nuclear receptor PPARγ 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 PPARγ 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 PPARγ-mediated control of the cell cycle and apoptosis depend on the recruitment of histone deacetylase 3 (HDAC3) to PPARγ. In combination, these data hence demonstrate that the effects of PPARγ on cell proliferation and apoptosis are dependent on the presence of an RB–HDAC3 complex.
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Acknowledgements
J-M Blanchard, C Sardet, and R Heyman are acknowledged for the gift of materials, and P Chambon, A Gandarillas, and the Auwerx lab for support and discussion. This work was supported by grants of CNRS, INSERM, Hôpital Universitaire de Strasbourg, ARC (#5800, #4724), the NIH Program project (1 P01-DK59820-01), and the European community RTD program (QLG1-CT-1999-00674).
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Fajas, L., Egler, V., Reiter, R. et al. PPARγ controls cell proliferation and apoptosis in an RB-dependent manner. Oncogene 22, 4186–4193 (2003). https://doi.org/10.1038/sj.onc.1206530
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DOI: https://doi.org/10.1038/sj.onc.1206530
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