Involvement of ZIP/p62 in the regulation of PPARα transcriptional activity by p38-MAPK

被引：12

作者：

Diradourian, Claire ^{[1
,2
]}

Le May, Cedric ^{[1
,2
]}

Cauezac, Michele ^{[1
,2
]}

Girard, Jean ^{[1
,2
]}

Burnol, Anne-Francoise ^{[1
,2
]}

Pegorier, Jean-Paul ^{[1
,2
]}

机构：

[1] Univ Paris 05, Inst Cochin, CNRS, UMR 8104, Paris, France

[2] INSERM, U567, Paris, France

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 2008年 / 1781卷 / 05期

关键词：

PPAR alpha; p38-MAPK; ZIP/p62; L-CPTI; phosphorylation; anisomycin; reporter gene; co-immunoprecipitation; siRNA; hepatoma cell;

D O I：

10.1016/j.bbalip.2008.02.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The peroxisome proliferator-activated receptor alpha (PPAR alpha) belongs to the nuclear receptor family and plays a central role in the regulation of lipid metabolism, glucose homeostasis and inflammatory processes. In addition to its ligand-induced activation, PPAR alpha is regulated by phosphorylation via ERK-MAPK, PKA and PKC. In this study we examined the effect of p38-MAPK on PPAR alpha transcriptional activity. In COS-7 cells, anisomycin, a p38 activator, induced a dose-dependent phosphorylation of PPAR alpha and a 50% inhibition of its transcriptional activity. In H4IIE hepatoma cells, anisomycin-induced p38 phosphorylation decreased both endogenous and PPAR alpha ligand-enhanced L-CPTI and ACO gene expression. Interestingly, PPAR alpha/p38 interaction required the molecular adapter ZIP/p62. Reducing ZIP/p62 expression by siRNA, partially reversed the inhibitory effect of anisomycin on L-CPTI gene expression. In conclusion, we showed that p38 activation induced PPAR alpha phosphorylation and inhibition of its transcriptional activity through a trimeric interaction between p38-MAPK, ZIP/p62 and PPAR alpha. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：239 / 244

页数：6

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