期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 291, 期 43, 页码 22757-22768出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M116.737387
关键词
apoptosis; phosphorylation; protein degradation; tyrosine-protein kinase (tyrosine kinase); ubiquitin ligase; BMX; Etk; N-end Rule
资金
- Natural Sciences and Engineering Research Council (NSERC) of Canada [341453-12]
- Alberta Innovates Technology Futures Graduate Student Scholarship
Cellular signaling leading to the initiation of apoptosis typically results in the activation of caspases, which in turn leads to the proteolytic generation of protein fragments with new or altered cellular functions. Increasing numbers of reports are demonstrating that the activity of many of these proteolytically activated protein fragments can be attenuated by their selective degradation by the N-end rule pathway. Here we report the first evidence that selective degradation of a caspase product by the N-end rule pathway can be modulated by phosphorylation. We demonstrate that the pro-apoptotic fragment of the bone marrow kinase on chromosome X (BMX) generated by caspase cleavage in the prostate cancer-derived PC3 cell line is metabolically unstable in cells because its N-terminal tryptophan targets it for proteasomal degradation via the N-end rule pathway. In addition, we have demonstrated that phosphorylation of tyrosine 566 relatively inhibits degradation of the C-terminal BMX catalytic fragment, and this phosphorylation is crucial for its pro-apoptotic function. Overall, our results demonstrate that cleaved BMX is a novel N-end rule substrate, and its degradation exhibits a novel interplay between substrate phosphorylation and N-end rule degradation, revealing an increasing complex regulatory network of apoptotic proteolytic signaling cascades.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据