Inflammasome-Activated Caspase 7 Cleaves PARP1 to Enhance the Expression of a Subset of NF-κB Target Genes
Inflammasome-Activated Caspase 7 Cleaves PARP1 to Enhance the Expression of a Subset of NF-κB Target Genes
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DOI：
10.1016/j.molcel.2012.02.016
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发表时间：
2012-04-27
期刊：
影响因子：
16
通讯作者：
Hottigert, Michael O.
中科院分区：
文献类型：
--
作者：
Erener, Sueheda;Petrilli, Virginie;Hottigert, Michael O.
Caspase1是炎症体的一部分，在病原体识别后组装，而Caspase3和/或7是凋亡和非凋亡功能的中介。PARP1裂解是细胞凋亡的一个标志，但不是必需的，这表明它还有另一个生理作用。在这里，我们证明了在内毒素刺激后，caspase7被caspase1激活，移位到细胞核，并在PARP1负调控的一组NF-kappa B靶基因的启动子上切割PARP1。突变PARP1裂解位点D214使PARP1不能被切割，并抑制PARP1从染色质和染色质解缩中释放，从而抑制切割依赖的NF-kappa B靶基因的表达。这些发现提出了caspase 7介导的PARP1裂解在促炎基因表达中的独立于细胞凋亡的调节作用，并为深入了解炎症体信号转导提供了洞察力。
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.