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Phosphorylation at tyrosine 262 promotes GADD34 protein turnover.

dc.contributor.author Jeyaraman, Krishna
dc.contributor.author Shenolikar, Shirish
dc.contributor.author Yusoff, Permeen
dc.contributor.author Zhou, Wei
dc.date.accessioned 2018-07-16T16:54:49Z
dc.date.available 2018-07-16T16:54:49Z
dc.date.issued 2013-11
dc.identifier.issn 0021-9258
dc.identifier.issn 1083-351X
dc.identifier.uri https://hdl.handle.net/10161/17230
dc.description.abstract In mammalian cells, metabolic and environmental stress increases the phosphorylation of the eukaryotic translational initiation factor, eIF2α, and attenuates global protein synthesis. Subsequent transcriptional activation of GADD34 assembles an eIF2α phosphatase that feeds back to restore mRNA translation. Active proteasomal degradation of GADD34 protein then reestablishes the sensitivity of cells to subsequent bouts of stress. Mass spectrometry established GADD34 phosphorylation on multiple serines, threonines, and tyrosines. Phosphorylation at tyrosine 262 enhanced the rate of the GADD34 protein turnover. Substrate-trapping studies identified TC-PTP (PTPN2) as a potential GADD34 phosphatase, recognizing phosphotyrosine 262. Reduced GADD34 protein levels in TC-PTP-null MEFs following ER stress emphasized the importance of TC-PTP in determining the cellular levels of GADD34 protein. The susceptibility of TC-PTP-null MEFs to ER stress-induced apoptosis was significantly ameliorated by ectopic expression of GADD34. The data suggested that GADD34 phosphorylation on tyrosine 262 modulates endoplasmic reticulum stress signaling and cell fate.
dc.language eng
dc.publisher AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.relation.ispartof The Journal of biological chemistry
dc.relation.isversionof 10.1074/jbc.m113.504407
dc.subject COS Cells
dc.subject Hela Cells
dc.subject Fibroblasts
dc.subject Animals
dc.subject Mice, Knockout
dc.subject Cercopithecus aethiops
dc.subject Humans
dc.subject Mice
dc.subject Tyrosine
dc.subject Signal Transduction
dc.subject Apoptosis
dc.subject Phosphorylation
dc.subject Embryo, Mammalian
dc.subject Protein Tyrosine Phosphatase, Non-Receptor Type 2
dc.subject Protein Phosphatase 1
dc.subject Endoplasmic Reticulum Stress
dc.subject Proteolysis
dc.title Phosphorylation at tyrosine 262 promotes GADD34 protein turnover.
dc.type Journal article
dc.date.updated 2018-07-16T16:54:46Z
pubs.begin-page 33146
pubs.end-page 33155
pubs.issue 46
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Psychiatry & Behavioral Sciences, Translational Neuroscience
pubs.organisational-group Psychiatry & Behavioral Sciences
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 288
duke.contributor.orcid Shenolikar, Shirish|0000-0003-0540-6328


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