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

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• 作者：Sü ; heda Erener¹ ; ² ; Virginie Pé ; trilli³ ; ⁴ ; Ingrid Kassner¹ ; ² ; Roberta Minotti¹ ; Rosa Castillo³ ; Raffaella Santoro¹ ; Paul  ; O. Hassa¹ ; Jü ; rg Tschopp³ ; Michael  ; O. Hottiger¹ ; ^{hottiger@vetbio.uzh.ch}
• 刊名：Molecular Cell
• 出版年：2012
• 期刊代码：111_10972765
• 类别：bio
• 出版时间：27 April, 2012
• 卷：46
• 期：2
• 页码：200-211
• 文件大小：1233 K

摘要

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Summary

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聽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-魏B target genes negatively regulated by PARP1. Mutating the PARP1 cleavage site D214 renders PARP1 uncleavable and聽inhibits PARP1 release from chromatin and chromatin decondensation, thereby restraining the expression of cleavage-dependent NF-魏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.