Substrate cleavage by caspases generates protein fragments with Smac/Diablo-like activities
Substrate cleavage by caspases generates protein fragments with Smac/Diablo-like activities
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DOI：
10.1038/sj.cdd.4401298
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发表时间：
2003-11-01
影响因子：
12.4
通讯作者：
Nicholson, DW
中科院分区：
文献类型：
--
作者：
Hell, K;Saleh, M;Nicholson, DW
Smac/Diablo 和 HtrA2/Omi 通过结合并拮抗 IAP 蛋白（包括“X 染色体连锁凋亡抑制剂”(XIAP)）来促进细胞凋亡。在这里，我们表明，半胱天冬酶介导的有限细胞死亡底物子集的蛋白水解在切割后暴露出功能性 Smac/Diablo 样 N 末端，这些 N 末端能够结合并拮抗 XIAP。我们认为，这种机制可能会建立细胞凋亡途径的前馈敏化，并有助于 IAP 拮抗作用的功能冗余。此外，这可能与阿尔茨海默氏病特别相关，因为 caspase 生成的 C31 肽（一种已确定的细胞毒素）在细胞凋亡处理后获得了 Smac/Diablo 样特性。
Smac/Diablo and HtrA2/Omi promote apoptosis by binding to and antagonizing IAP proteins, including the 'X chromosome-linked inhibitor of apoptosis' (XIAP). Here we show that caspase-mediated proteolysis of a limited subset of cell death substrates exposes functional Smac/Diablo-like N-termini after cleavage, which are able to bind to and antagonize XIAP. We propose that this mechanism may establish a feedforward sensitization of the apoptotic pathway and contribute to the functional redundancy of IAP antagonism. In addition, this may be particularly relevant in Alzheimer's disease since the caspase-generated C31 peptide, an established cytotoxin, acquires Smac/Diablo-like properties after apoptotic processing.