Bcl-2 and Bcl-XL regulate proinf lammatory caspase-1 activation by interaction with NALP1

被引：281

作者：

Bruey, Jean-Marie ^{[1
]}

Bruey-Sedano, Nathalie ^{[1
]}

Luciano, Frederic ^{[1
]}

Zhai, Dayong ^{[1
]}

Balpai, Ruchi ^{[1
]}

Xu, Chunyan ^{[1
]}

Kress, Christina L. ^{[1
]}

Bailly-Maitre, Beatrice ^{[1
]}

Li, Xiaoqing ^{[1
]}

Osterman, Andrei ^{[1
]}

Matsuzawa, Shu-ichi ^{[1
]}

Terskikh, Alexey V. ^{[1
]}

Faustin, Benjamin ^{[1
]}

Reed, John C. ^{[1
]}

机构：

[1] Burnham Inst Med Res, La Jolla, CA 92037 USA

来源：

CELL | 2007年 / 129卷 / 01期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.cell.2007.01.045

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：

Caspases are intracellular proteases that cleave substrates involved in apoptosis or inflammation. In C. elegans, a paradigm for caspase regulation exists in which caspase CED-3 is activated by In ucleotide-binding protein CED-4, which is suppressed by Bcl-2-family protein CED-9. We have identified a mammalian analog of this caspase-regulatory system in the NLR-family protein NALP1, a nucleotide-dependent activator of cytokine-processing protease caspase-1, which responds to bacterial ligand muramyl-dipeptide (MDP). Antiapoptotic proteins Bcl-2 and Bcl-X-L bind and suppress NALP1, reducing caspase-1 activation and interleukin-1 beta (IL-1 beta) production. When exposed to MDP, Bcl-2-deficient macrophages exhibit more caspase-1 processing and IL-1 beta production, whereas Bcl-2-overexpressing macrophages demonstrate less caspase-1 processing and IL-1 beta production. The findings reveal an interaction of host defense and apoptosis machinery.

引用

页码：45 / 56

页数：12

共 32 条

[11] NACHT-LRR proteins (NLRs) in bacterial infection and immunity [J].