Different ways to regulate the PPARα stability
Different ways to regulate the PPARα stability
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DOI：
10.1016/j.bbrc.2004.05.035
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发表时间：
2004-06-25
影响因子：
3.1
通讯作者：
Glineur, C
中科院分区：
文献类型：
--
作者：
Blanquart, C;Mansouri, R;Glineur, C
过氧化物酶体增殖体激活受体是一种配体激活的转录因子。ppar调节脂质和葡萄糖代谢并控制炎症反应。最近，我们发现ppar是一种被泛素-蛋白酶体系统降解的短寿命蛋白。在这项研究中，我们分析了与rxrα、CBP和N-CoR相互作用的影响，以及磷酸化对ppar泛素化和稳定性的影响。我们的研究结果表明，ppar α与rxr α或CBP的相互作用导致蛋白质周转增加。相反，与协同抑制因子N-CoR相互作用，抑制其转录活性，导致蛋白质稳定。有趣的是，用已知会导致pparα过度磷酸化的丝氨酸/苏氨酸磷酸酶抑制剂处理细胞，可诱导其转录活性，并伴有蛋白质的稳定。这些数据表明，异源二聚化、辅因子的募集和翻译后修饰可以调节ppar - α的稳定性。(C) 2004爱思唯尔公司版权所有。
Peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-activated transcription factor. PPARalpha regulates lipid and glucose metabolism and controls the inflammatory response. Recently, we have shown that PPARalpha is a short-lived protein degraded by the ubiquitin-proteasome system. In this study, we have analysed the effects of interaction with RXRalpha, CBP, and N-CoR and also the implication of phosphorylation on ubiquitination and stability of PPARalpha. Our results show that interaction of PPARalpha with RXRalpha or CBP leads to an increase in the turnover of the protein. In contrast, interaction with the corepressor N-CoR, which inhibits its transcriptional activity, leads to a stabilization of the protein. Interestingly, treatment of cells with an inhibitor of Ser/Thr phosphatases known to lead to hyperphosphorylation of PPARalpha induces its transcriptional activity which is accompanied by a stabilization of the protein. These data indicate that heterodimerization, recruitment of cofactors, and post-translational modifications can modulate the stability of PPARalpha. (C) 2004 Elsevier Inc. All rights reserved.