The modulation of PPARγ proteins by caspases
Abstract
PPARγ is a transcription factor that plays an important role in adipocyte gene expression. Previous studies from our laboratory and others have shown that PPARγ can be ubiquitin modified and targeted to the proteasome for degradation in response to transcriptional activation or exposure to interferonγ. In this study, we examined the TNFα induced degradation of PPARγ proteins in cultured 3T3-L1 adipocytes. We observed that TNFα could induce a caspase-mediated degradation of PPARγ proteins in the presence ofcyclohexmide. The caspase-mediated degradation of PPARγ resulted in the generation of a highly specific PPAKγ cleavage product. Moreover, the generation of the caspase induced PPARγ cleavage product was not inhibited by a specific proteasome inhibitor, but was repressed by a caspase inhibitor. Caspase 6, which has been implicated to play a role in Akt degradation in fat cells, did not appear to be involved in PPARγ degradation. We also examined the effects of a TZD, salicylate and vanadate on the degradation of PPARγ proteins in adipocytes. In summary, our results demonstrate that PPARγ proteins can be degraded by the proteasome and by caspases under specific conditions in cultured adipocytes. Copyright © 2006 by New Century Health Publishers, LLC.