Mammalian proapoptotic factor ChaC1 and its homologues function as γ-glutamyl cyclotransferases acting specifically on glutathione.
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 γ-glutamyl cyclotransferases acting specifically to degrade glutathione but not other γ-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.
CSIR-Institute of Microbial Technology, Sector 39-A, Chandigarh 160036, India.
Akhilesh
A
Kumar
Shweta
S
Tikoo
Shuvadeep
S
Maity
Shantanu
S
Sengupta
Sagar
S
Sengupta
Amandeep
A
Kaur
Anand Kumar
AK
Bachhawat
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D020134:Catalytic Domain; D059865:Endoplasmic Reticulum Stress; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005786:Gene Expression Regulation; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D033921:Vesicular Transport Proteins; D005723:gamma-Glutamyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D009419:Nerve Tissue Proteins; D010455:Peptides; D033921:Vesicular Transport Proteins; C497828:Vps13a protein, mouse; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid