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Title: Phosphorylation at tyrosine 262 promotes GADD34 protein turnover
Authors: Zhou, W.
Jeyaraman, K.
Yusoff, P.
Shenolikar, S. 
Issue Date: 15-Nov-2013
Citation: Zhou, W., Jeyaraman, K., Yusoff, P., Shenolikar, S. (2013-11-15). Phosphorylation at tyrosine 262 promotes GADD34 protein turnover. Journal of Biological Chemistry 288 (46) : 33146-33155. ScholarBank@NUS Repository.
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 restoremRNAtranslation. 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 potentialGADD34phosphatase, recognizing phosphotyrosine 262. ReducedGADD34protein 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. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
ISSN: 00219258
DOI: 10.1074/jbc.M113.504407
Appears in Collections:Staff Publications

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