Characterization of BAG3 cleavage during apoptosis of pancreatic cancer cells
Characterization of BAG3 cleavage during apoptosis of pancreatic cancer cells
复制标题
DOI：
10.1002/jcp.22097
复制
发表时间：
2010-07
影响因子：
5.6
通讯作者：
Hua-Qin Wang;Xin Meng;Yan-Yan Gao-Yan;Bao-qin Liu;Xiao-Fang Niu;Hai-yan Zhang;Zhen‐Xian Du
中科院分区：
文献类型：
--
作者：
Hua-Qin Wang;Xin Meng;Yan-Yan Gao-Yan;Bao-qin Liu;Xiao-Fang Niu;Hai-yan Zhang;Zhen‐Xian Du
半胱天冬酶是细胞死亡蛋白酶的保守家族，其在Asp残基处切割细胞内底物以改变其功能并促进凋亡。在这份报告中，我们确定BAG 3作为一种新的caspase底物。在这里，我们表明，这些BAG蛋白之一，BAG 3，在细胞凋亡过程中被切割。BAG 3裂解被几种不同的半胱天冬酶抑制剂抑制。通过重组半胱天冬酶蛋白对BAG 3裂解的分析显示，BAG 3被半胱天冬酶-3有效裂解，在较小程度上被半胱天冬酶-1和半胱天冬酶-8裂解，并且被半胱天冬酶-9裂解相对低效。在体外和胰腺癌SW 1990和PANC-1细胞中，BAG 3蛋白的切割主要发生在蛋白的C末端部分，主要位于Asp 347（KEVD 347 ↓S）。我们还证明，与Bcl-2和Bcl-XL的切割不同，BAG 3的切割形式不会导致促凋亡片段，然而，BAG 3的切割导致其本身抗凋亡特性的丧失。BAG 3的这种新的调节可能对其在细胞凋亡中的作用具有重要意义。J.细胞。Physiol. 224：94-100，2010 © 2010 Wiley利斯公司
Caspases are a conserved family of cell death proteases that cleave intracellular substrates at Asp residues to modify their function and promote apoptosis. In this report, we identify BAG3 as a novel caspases substrate. Here, we show that one of these BAG proteins, BAG3, is cleaved during apoptosis. BAG3 cleavage is inhibited by several different caspase inhibitors. The analysis of BAG3 cleavage by recombinant caspase proteins shows that BAG3 is efficiently cleaved by caspase‐3, to a smaller extent by caspases‐1 and ‐8, and relatively inefficient by caspase‐9. Cleavage of the BAG3 protein occurs in the C‐terminal part of the protein majorly at Asp347 (KEVD347↓S) in vitro and in pancreatic cancer SW1990 and PANC‐1 cells undergoing apoptosis. We also demonstrate that unlike cleavage of Bcl‐2 and Bcl‐XL, cleaved form of BAG3 does not result in pro‐apoptotic fragments, however, cleavage of BAG3 lead to loss its per se anti‐apoptotic property. This novel regulation of BAG3 may have important implications for its role in apoptosis. J. Cell. Physiol. 224:94–100, 2010 © 2010 Wiley‐Liss, Inc.