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J Biol Chem DOI:10.1074/jbc.M117.797084

Lysine trimethylation regulates 78-kDa glucose-regulated protein proteostasis during endoplasmic reticulum stress.

Publication TypeJournal Article
Year of Publication2017
AuthorsSieber, J, Wieder, N, Ostrosky-Frid, M, Dvela-Levitt, M, Aygun, O, Udeshi, ND, Carr, SA, Greka, A
JournalJ Biol Chem
Volume292
Issue46
Pages18878-18885
Date Published2017 11 17
ISSN1083-351X
KeywordsAnimals, Cell Line, DNA Modification Methylases, Endoplasmic Reticulum Stress, Heat-Shock Proteins, Lysine, Methylation, Mice, Podocytes, Proteolysis, Unfolded Protein Response
Abstract

The up-regulation of chaperones such as the 78-kDa glucose-regulated protein (GRP78, also referred to as BiP or HSPA5) is part of the adaptive cellular response to endoplasmic reticulum (ER) stress. GRP78 is widely used as a marker of the unfolded protein response, associated with sustained ER stress. Here we report the discovery of a proteostatic mechanism involving GRP78 trimethylation in the context of ER stress. Using mass spectrometry-based proteomics, we identified two GRP78 fractions, one homeostatic and one induced by ER stress. ER stress leads to biosynthesis of non-trimethylated GRP78, whereas homeostatic, METTL21A-dependent lysine 585-trimethylated GRP78 is reduced. This proteostatic mechanism, dependent on the posttranslational modification of GRP78, allows cells to differentially regulate specific protein abundance during cellular stress.

DOI10.1074/jbc.M117.797084
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/28912266?dopt=Abstract

Alternate JournalJ. Biol. Chem.
PubMed ID28912266
PubMed Central IDPMC5704472