Endoplasmic reticulum stress differentially inhibits endoplasmic reticulum and inner nuclear membrane protein quality control degradation pathways.

Autor:	Buchanan BW; Department of Biology, Ball State University, Muncie, Indiana 47306., Mehrtash AB; Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520., Broshar CL; Department of Biology, Ball State University, Muncie, Indiana 47306., Runnebohm AM; Department of Biology, Ball State University, Muncie, Indiana 47306., Snow BJ; Department of Biology, Ball State University, Muncie, Indiana 47306., Scanameo LN; Department of Biology, Ball State University, Muncie, Indiana 47306., Hochstrasser M; Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520., Rubenstein EM; Department of Biology, Ball State University, Muncie, Indiana 47306 emrubenstein@bsu.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2019 Dec 20; Vol. 294 (51), pp. 19814-19830. Date of Electronic Publication: 2019 Nov 13.
DOI:	10.1074/jbc.RA119.010295
Abstrakt:	Endoplasmic reticulum (ER) stress occurs when the abundance of unfolded proteins in the ER exceeds the capacity of the folding machinery. Despite the expanding cadre of characterized cellular adaptations to ER stress, knowledge of the effects of ER stress on cellular physiology remains incomplete. We investigated the impact of ER stress on ER and inner nuclear membrane protein quality control mechanisms in Saccharomyces cerevisiae. We analyzed the turnover of substrates of four ubiquitin ligases (Doa10, Rkr1/Ltn1, Hrd1, and the Asi complex) and the metalloprotease Ste24 in induced models of ER stress. ER stress did not substantially impact Doa10 or Rkr1 substrates. However, Hrd1-mediated destruction of a protein that aberrantly engages the translocon ( Deg1 -Sec62) and substrates with luminal degradation signals was markedly impaired by ER stress; by contrast, Hrd1-dependent degradation of proteins with intramembrane degrons was largely unperturbed by ER stress. ER stress impaired the degradation of one of two Asi substrates analyzed and caused a translocon-clogging Ste24 substrate to accumulate in a form consistent with persistent translocon occupation. Degradation of Deg1 -Sec62 in the absence of stress and stabilization during ER stress were independent of four ER stress-sensing pathways. Our results indicate ER stress differentially impacts degradation of protein quality control substrates, including those mediated by the same ubiquitin ligase. These observations suggest the existence of additional regulatory mechanisms dictating substrate selection during ER stress. (© 2019 Buchanan et al.)
Databáze:	MEDLINE
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