Lysine trimethylation regulates 78 kDa glucose-regulated protein proteostasis during endoplasmic reticulum stress [Genomics and Proteomics]

The upregulation 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 de novo biosynthesis of non-trimethylated GRP78, while homeostatic, METTL21A-dependent lysine 585 trimethylated GRP78 is reduced. This proteostatic mechanism, dependent on the post-translational modification of GRP78, allows cells to differentially regulate specific protein abundance during cellular stress.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wdxofD
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