Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics*
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Catalytic Domain
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Endoplasmic Reticulum Stress
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Escherichia coli / enzymology
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Escherichia coli / genetics
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Gene Expression Regulation
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Glutathione* / chemistry
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Glutathione* / metabolism
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Mice
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Nerve Tissue Proteins* / chemistry
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Nerve Tissue Proteins* / genetics
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Nerve Tissue Proteins* / metabolism
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Peptides / metabolism
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Protein Conformation
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Protein Folding
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Pyrrolidonecarboxylic Acid / chemistry
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Pyrrolidonecarboxylic Acid / metabolism
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Saccharomyces cerevisiae / enzymology
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Saccharomyces cerevisiae / genetics
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Vesicular Transport Proteins
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gamma-Glutamyltransferase* / chemistry
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gamma-Glutamyltransferase* / genetics
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gamma-Glutamyltransferase* / metabolism
Substances
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Nerve Tissue Proteins
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Peptides
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Vesicular Transport Proteins
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Vps13a protein, mouse
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gamma-Glutamyltransferase
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Glutathione
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Pyrrolidonecarboxylic Acid