Inflammasome-Activated Caspase 7 Cleaves PARP1 to Enhance the Expression of a Subset of NF-κB Target Genes

被引：163

作者：

Erener, Sueheda ^{[1
,2
]}

Petrilli, Virginie ^{[3
]}

Kassner, Ingrid ^{[1
,2
]}

Minotti, Roberta ^{[1
]}

Castillo, Rosa

Santoro, Raffaella ^{[1
]}

Hassa, Paul O. ^{[1
]}

Tschopp, Juerg ^{[3
]}

Hottigert, Michael O. ^{[1
]}

机构：

[1] Univ Zurich, Inst Vet Biochem & Mol Biol, CH-8057 Zurich, Switzerland

[2] Univ Zurich, Mol Life Sci Program, Life Sci Zurich Grad Sch, CH-8057 Zurich, Switzerland

[3] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

来源：

MOLECULAR CELL | 2012年 / 46卷 / 02期

基金：

瑞士国家科学基金会;

关键词：

POLY(ADP-RIBOSE) POLYMERASE-1; TRANSCRIPTION; APOPTOSIS; CHROMATIN; PROTEIN; CARM1; CELLS; COACTIVATION; RESPONSES; NLRP3;

D O I：

10.1016/j.molcel.2012.02.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Caspase 1 is part of the inflammasome, which is assembled upon pathogen recognition, while caspases 3 and/or 7 are mediators of apoptotic and nonapoptotic functions. PARP1 cleavage is a hallmark of apoptosis yet not essential, suggesting it has another physiological role. Here we show that after LPS stimulation, caspase 7 is activated by caspase 1, translocates to the nucleus, and cleaves PARP1 at the promoters of a subset of NF-kappa B target genes negatively regulated by PARP1. Mutating the PARP1 cleavage site D214 renders PARP1 uncleavable and inhibits PARP1 release from chromatin and chromatin decondensation, thereby restraining the expression of cleavage-dependent NF-kappa B target genes. These findings propose an apoptosis-independent regulatory role for caspase 7-mediated PARP1 cleavage in proinflammatory gene expression and provide insight into inflammasome signaling.

引用

页码：200 / 211

页数：12

共 45 条

[1]

Caspase-7 Activation by the Nlrc4/Ipaf Inflammasome Restricts Legionella pneumophila Infection [J].