You are here

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
Date Published2017 11 17
KeywordsAnimals, Cell Line, DNA Modification Methylases, Endoplasmic Reticulum Stress, Heat-Shock Proteins, Lysine, Methylation, Mice, Podocytes, Proteolysis, Unfolded Protein Response

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.


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