PXD025726

PXD025726 is an original dataset announced via ProteomeXchange.

Title	E2 Rad6 controls cellular response to oxidative stress
Description	Protein ubiquitination is an essential process that rapidly regulates protein synthesis, function, and fate in dynamic environments. Among its non-proteolytic functions, K63 ubiquitin accumulates in yeast cells exposed to oxidative stress, stalling ribosomes at elongation. K63 ubiquitin conjugates accumulate because of redox inhibition of the deubiquitinating enzyme Ubp2, however, the role and regulation of ubiquitin conjugating enzymes in this pathway remained unclear. Here we found that the E2 Rad6 binds and modifies elongating ribosomes during oxidative stress. We elucidated a mechanism by which Rad6 and its human homolog UBE2A are redox-regulated by forming reversible disulfides with the E1 activating enzyme, Uba1. We further showed that Rad6 activity is necessary to regulate translation, antioxidant defense, and adaptation to stress. Finally, we showed that Rad6 is required to induce phosphorylation of the translation initiation factor eIF2α, providing a novel link for K63 ubiquitin, elongation stalling, and the integrated stress response.
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-11_23:56:37.836.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gustavo Silva
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-30 00:39:23	ID requested
⏵ 1	2022-08-11 23:56:38	announced

Sim, õ, es V, Cizubu BK, Harley L, Zhou Y, Pajak J, Snyder NA, Bouvette J, Borgnia MJ, Arya G, Bartesaghi A, Silva GM, Redox-sensitive E2 Rad6 controls cellular response to oxidative stress via K63-linked ubiquitination of ribosomes. Cell Rep, 39(8):110860(2022) [pubmed]

submitter keyword: Rad6, K63 ubiquitin, E1, yeast, oxidative stress

Gustavo Silva
contact affiliation	Duke University, Department of Biology, USA
contact email	gustavo.silva@duke.edu
lab head
Gustavo Silva
contact affiliation	Duke University
contact email	gustavo.silva@duke.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025726
     1. Label: PRIDE project
     2. Name: E2 Rad6 controls cellular response to oxidative stress