Endoplasmic reticulum (ER) chaperone regulation and survival of cells compensating for deficiency in the ER stress response kinase, PERK.

The Journal of Biological Chemistry
Yukihiro YamaguchiPeter Arvan

Abstract

The activity of PERK, an endoplasmic reticulum (ER) transmembrane protein kinase, assists in an ER stress response designed to inhibit general protein synthesis while allowing upregulated synthesis of selective proteins such as the ATF4 transcription factor. PERK null mice exhibit phenotypes that especially affect secretory cell types. Although embryonic fibroblasts from these mice are difficult to transfect with high efficiency, we have generated 293 cells stably expressing the PERK-K618A dominant negative mutant. 293/PERK-K618A cells, in response to ER stress: (a) do not properly inhibit general protein synthesis, (b) exhibit defective/delayed induction of ATF4 and BiP, and (c) exhibit exuberant splice activation of XBP1 and robust cleavage activation of ATF6, with abnormal regulation of calreticulin levels. The data suggest compensatory mechanisms allowing for cell survival in the absence of functional PERK. Interestingly, although induction of CHOP (a transcription factor implicated in apoptosis) is notably delayed after onset of ER stress, 293/PERK-K618A cells eventually produce CHOP at normal or even supranormal levels and exhibit increased apoptosis either in response to general ER stress or, more importantly, to specifi...Continue Reading

References

Jan 19, 1999·Annual Review of Cell and Developmental Biology·R ChapmanP Walter
Aug 23, 2000·The Journal of Cell Biology·K NakamuraM Michalak
Aug 30, 2001·Proceedings of the National Academy of Sciences of the United States of America·S OyadomariM Mori
Feb 21, 2002·The Journal of Clinical Investigation·David Ron
Feb 21, 2002·The Journal of Clinical Investigation·Seiichi OyadomariMasataka Mori
Jun 28, 2002·Swiss Medical Weekly·Jonas Rutishauser, Martin Spiess
Feb 15, 2003·Developmental Cell·Hiderou YoshidaKazutoshi Mori
Mar 4, 2003·Nature Reviews. Molecular Cell Biology·Lars Ellgaard, Ari Helenius
Jun 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ying WuRichard N Sifers
Feb 12, 2005·The Journal of Biological Chemistry·Ming LiuPeter Arvan
Apr 12, 2005·Cell·Yoshiki SekijimaJeffery W Kelly
Jun 15, 2005·Annual Review of Biochemistry·Martin Schröder, Randal J Kaufman
Aug 2, 2005·Nature Cell Biology·Birgit MeusserThomas Sommer
Oct 4, 2006·Physiological Reviews·Stefan J Marciniak, David Ron

❮ Previous
Next ❯

Citations

Jul 18, 2012·Cell Stress & Chaperones·Sayuri TakayanagiKenichi Yoshida
May 10, 2013·ACS Synthetic Biology·Spencer C AlfordRobert E Campbell
Jun 19, 2012·Cell Death and Differentiation·T VerfaillieP Agostinis
Feb 10, 2010·Omics : a Journal of Integrative Biology·Xiaowei WuJianguo Zhang
Oct 10, 2012·Journal of Plant Physiology·Yuhya WakasaFumio Takaiwa
May 24, 2011·The International Journal of Biochemistry & Cell Biology·Geum-Hwa LeeHyung-Ryong Kim
Aug 21, 2010·Trends in Endocrinology and Metabolism : TEM·Ming LiuPeter Arvan
Aug 25, 2010·Cancer Letters·Tom VerfailliePatrizia Agostinis
Oct 20, 2009·European Journal of Pharmacology·Sandra J M HealyAfshin Samali
Jan 13, 2011·The Plant Journal : for Cell and Molecular Biology·Yuhya WakasaFumio Takaiwa
Oct 22, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Seul Ki LimSoo Hyun Park
Apr 21, 2016·ASN Neuro·Nicolò MusnerLawrence Wrabetz
Jan 22, 2013·Toxicologic Pathology·Marc A LafleurJeffrey W Lawrence
Mar 25, 2017·Journal of Alzheimer's Disease : JAD·Xin-Jun LiuFeng-Xue Lao
Sep 24, 2019·Cell Metabolism·Sifan ChenSudha B Biddinger

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis