Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Sieber, J, Wieder, N, Ostrosky-Frid, M, Dvela-Levitt, M, Aygun, O, Udeshi, ND, Carr, SA, Greka, A |
Journal | J Biol Chem |
Volume | 292 |
Issue | 46 |
Pages | 18878-18885 |
Date Published | 2017 11 17 |
ISSN | 1083-351X |
Keywords | Animals, 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. |
DOI | 10.1074/jbc.M117.797084 |
Pubmed | |
Alternate Journal | J. Biol. Chem. |
PubMed ID | 28912266 |
PubMed Central ID | PMC5704472 |
J Biol Chem DOI:10.1074/jbc.M117.797084
Lysine trimethylation regulates 78-kDa glucose-regulated protein proteostasis during endoplasmic reticulum stress.
Recent Broad Publications
News at the broad
News / 12.7.22
News / 01.12.23