Redox control of the deubiquitinating enzyme Ubp2 regulates translation during stress

Author:

Santos Clara M.,Cizubu Blanche K.,Okonkwo Dinachi,Chen Chia-Yu,Maske Natori,Snyder Nathan A.,Simoes Vanessa,Washington Erica J.,Silva Gustavo M.

Abstract

AbstractProtein ubiquitination is essential to govern cell’s ability to cope with harmful environments by regulating many aspects of protein dynamics from synthesis to degradation. As important as the ubiquitination process, the reversal of ubiquitin chains mediated by deubiquitinating enzymes (DUBs) is critical for proper recovery from stress and re-establishment of proteostasis. Although it is known that ribosomes are decorated with K63-linked polyubiquitin (K63-ub) chains that control protein synthesis under stress, the mechanisms by which these ubiquitin chains are reversed and regulate proteostasis during stress recovery are still illusive. Here, we showed in budding yeast that the DUB Ubp2 is redox regulated during oxidative stress in a reversible manner, which determines the levels of K63-ub chains present on ribosomes. We also demonstrate that Ubp2 is a processive enzyme whose activity is modulated by a series of repeated domains and the formation of important disulfide bonds. By combining, cellular, biochemical, and proteomics analyses, we showed that Ubp2 is crucial for restoring translation after stress cessation, indicating an important role in determining cellular response to oxidative stress. Our work demonstrates a novel role for Ubp2, revealing that a range of signaling pathways can be controlled by redox regulation of DUB activity in eukaryotes, which in turn will define cellular states of health and diseases.

Publisher

Cold Spring Harbor Laboratory

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