Mammalian proapoptotic factor ChaC1 and its homologues function as γ-glutamyl cyclotransferases acting specifically on glutathione

被引：163
作者：
Kumar, Akhilesh [1 ]
Tikoo, Shweta [2 ]
Maity, Shuvadeep
Sengupta, Shantanu
Sengupta, Sagar [2 ]
Kaur, Amandeep [3 ,4 ]
Bachhawat, Anand Kumar [1 ,3 ,4 ]
机构：
[1] CSIR, Inst Microbial Technol, Chandigarh 160036, India
[2] Natl Inst Immunol, New Delhi 110067, India
[3] CSIR, Insitute Genom & Integrat Biol, New Delhi 110007, India
[4] Indian Inst Sci Educ & Res Mohali, Dept Biol Sci, Manauli, Punjab, India
来源：
EMBO REPORTS | 2012年 / 13卷 / 12期
关键词：
apoptosis; ChaC1; gamma-glutamyl cyclotransferases; glutathione; 5-oxoproline; ENDOPLASMIC-RETICULUM STRESS; SACCHAROMYCES-CEREVISIAE; APOPTOSIS; IDENTIFICATION; ENZYME; CELLS; DEPLETION; CYCLE;
D O I：
10.1038/embor.2012.156
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：
ChaC1 is a mammalian proapoptic protein of unknown function induced during endoplasmic reticulum stress. We show using in vivo studies and novel in vitro assays that the ChaC family of proteins function as gamma-glutamyl cyclotransferases acting specifically to degrade glutathione but not other gamma-glutamyl peptides. The overexpression of these proteins (but not the catalytically dead E>Q mutants) led to glutathione depletion and enhanced apoptosis in yeast. The ChaC family is conversed across all phyla and represents a new pathway for glutathione degradation in living cells, and the first cytosolic pathway for glutathione degradation in mammalian cells.
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收藏
页码：1095 / 1101
页数：7
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