Characterisation of Mcl-1 cleavage during apoptosis of haematopoietic cells

被引:72
作者
Clohessy, JG [1 ]
Zhuang, JG [1 ]
Brady, HJM [1 ]
机构
[1] UCL, Inst Child Hlth, Mol Haematol & Canc Biol Unit, London WC1N 1EH, England
关键词
apoptosis; Mcl-1; caspase; Bcl-2; haematopoiesis;
D O I
10.1111/j.1365-2141.2004.04949.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mcl-1 is essential for normal haematopoiesis, being required for lymphocyte development and maintenance. Its role in haematopoietic differentiation and development is associated with its function as an anti-apoptotic member of the Bcl-2 family of proteins although the underlining mechanism is poorly understood. We have characterized caspase cleavage of the Mcl-1 protein during apoptosis. Caspase cleavage resulted in the removal of the PEST regions from the protein and generation of a fragment containing the BH-1, -2 and -3 homology domains. Removal of the PEST regions did not appear to alter Mcl-1 stability, suggesting that these regions are not responsible for Mcl-1's short half-life. In addition, unlike cleavage of Bcl-2 and Bcl-X-L, which resulted in pro-apoptotic fragments, cleaved forms of Mcl-1 were unable to induce apoptosis. This novel regulation of Mcl-1 may have important implications not only for its role in apoptosis but also for the essential role it plays in the differentiation and development of haematopoietic cells.
引用
收藏
页码:655 / 665
页数:11
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