PPARgamma controls cell proliferation and apoptosis in an RB-dependent manner.
The nuclear receptor PPARgamma 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 PPARgamma 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 PPARgamma-mediated control of the cell cycle and apoptosis depend on the recruitment of histone deacetylase 3 (HDAC3) to PPARgamma. In combination, these data hence demonstrate that the effects of PPARgamma on cell proliferation and apoptosis are dependent on the presence of an RB-HDAC3 complex.
Fajas
Lluis
L
Institut de Génétique et de Biologie Moléculaire et Cellulaire/CNRS/INSERM/ULP, 67404 Illkirch, France.
Egler
Viviane
V
Reiter
Raphael
R
Miard
Stéphanie
S
Lefebvre
Anne-Marie
AM
Auwerx
Johan
J
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002453:Cell Cycle; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase; D016195:G2 Phase; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008938:Mitosis; D009369:Neoplasms / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D034741:RNA, Small Interfering / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D000099186:Histone Deacetylase 3
D001973:Bromodeoxyuridine; D006655:Histone Deacetylases; D008156:Luciferases; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D016160:Retinoblastoma Protein; D000077154:Rosiglitazone; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000099186:Histone Deacetylase 3