p58IPK is an inhibitor of the eIF2α kinase GCN2 and its localization and expression underpin protein synthesis and ER processing capacity

2015 ◽  
Vol 465 (2) ◽  
pp. 213-225 ◽  
Author(s):  
Anne Roobol ◽  
Jo Roobol ◽  
Amandine Bastide ◽  
John R. P. Knight ◽  
Anne E. Willis ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Synthesis ◽  
Cellular Stress ◽  
Processing Capacity ◽  
General Inhibitor ◽  
Eif2α Kinase

We show that p58IPK is a general inhibitor of the eIF2α kinases and its expression and localization are important in the capacity of the cells to respond to cellular stress by controlling protein synthesis rates and subsequent folding in the endoplasmic reticulum.

Spatial localization of unknown proteins in the endoplasmic reticulum predicts functions

2007 ◽  
Vol 30 (4) ◽  
pp. 84
Author(s):  
Michael D. Jain ◽  
Hisao Nagaya ◽  
Annalyn Gilchrist ◽  
Miroslaw Cygler ◽  
John J.M. Bergeron
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Protein Synthesis ◽  
Protein Function ◽  
Protein Translocation ◽  
Spatial Localization ◽  
Predict Protein Function ◽  
Insight Into ◽  
Soluble Fractions ◽  
Er Membrane

Protein synthesis, folding and degradation functions are spatially segregated in the endoplasmic reticulum (ER) with respect to the membrane and the ribosome (rough and smooth ER). Interrogation of a proteomics resource characterizing rough and smooth ER membranes subfractionated into cytosolic, membrane, and soluble fractions gives a spatial map of known proteins involved in ER function. The spatial localization of 224 identified unknown proteins in the ER is predicted to give insight into their function. Here we provide evidence that the proteomics resource accurately predicts the function of new proteins involved in protein synthesis (nudilin), protein translocation across the ER membrane (nicalin), co-translational protein folding (stexin), and distal protein folding in the lumen of the ER (erlin-1, TMX2). Proteomics provides the spatial localization of proteins and can be used to accurately predict protein function.

scholarly journals Fluoride Induces Endoplasmic Reticulum Stress and Inhibits Protein Synthesis and Secretion

2008 ◽  
Vol 116 (9) ◽  
pp. 1142-1146 ◽  
Author(s):  
Ramaswamy Sharma ◽  
Masahiro Tsuchiya ◽  
John D. Bartlett
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Synthesis ◽  
Endoplasmic Reticulum Stress

scholarly journals Differential regulation of cellular stress responses by the endoplasmic reticulum-resident Selenoprotein S (Seps1) in proliferating myoblasts versus myotubes

2018 ◽  
Vol 6 (24) ◽  
pp. e13926 ◽  
Author(s):  
Alex B. Addinsall ◽  
Sheree D. Martin ◽  
Fiona Collier ◽  
Xavier A. Conlan ◽  
Victoria C. Foletta ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Responses ◽  
Cellular Stress ◽  
Differential Regulation ◽  
Selenoprotein S ◽  
Cellular Stress Responses

Protein Synthesis on Endoplasmic Reticulum

1983 ◽  
pp. 143-145
Author(s):  
Odd Nygård ◽  
Peter Westermann
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Synthesis

Sweetened kallikrein-related peptidases (KLKs): glycan trees as potential regulators of activation and activity

2014 ◽  
Vol 395 (9) ◽  
pp. 959-976 ◽  
Author(s):  
Shihui Guo ◽  
Wolfgang Skala ◽  
Viktor Magdolen ◽  
Hans Brandstetter ◽  
Peter Goettig
Keyword(s):  
Prostate Cancer ◽  
Endoplasmic Reticulum ◽  
Protein Synthesis ◽  
Benign Prostatic Hyperplasia ◽  
Active Site ◽  
Prostatic Hyperplasia ◽  
Healthy Individuals ◽  
Glycosylation Pattern ◽  
Structural Stabilization ◽  
Respective Function

Abstract Most kallikrein-related peptidases (KLKs) are N-glycosylated with N-acetylglucosamine2-mannose9 units at Asn-Xaa-Ser/Thr sequons during protein synthesis and translocation into the endoplasmic reticulum. These N-glycans are modified in the Golgi machinery, where additional O-glycosylation at Ser and Thr takes place, before exocytotic release of the KLKs into the extracellular space. Sequons are present in all 15 members of the KLKs and comparative studies for KLKs from natural and recombinant sources elucidated some aspects of glycosylation. Although glycosylation of mammalian KLKs 1, 3, 4, 6, and 8 has been analyzed in great detail, e.g., by crystal structures, the respective function remains largely unclear. In some cases, altered enzymatic activity was observed for KLKs upon glycosylation. Remarkably, for KLK3/PSA, changes in the glycosylation pattern were observed in samples of benign prostatic hyperplasia and prostate cancer with respect to healthy individuals. Potential functions of KLK glycosylation in structural stabilization, protection against degradation, and activity modulation of substrate specificity can be deduced from a comparison with other glycosylated proteins and their regulation. According to the new concept of protein sectors, glycosylation distant from the active site might significantly influence the activity of proteases. Novel pharmacological approaches can exploit engineered glycans in the therapeutical context.

Emerging roles of endoplasmic reticulum-resident selenoproteins in the regulation of cellular stress responses and the implications for metabolic disease

2018 ◽  
Vol 475 (6) ◽  
pp. 1037-1057 ◽  
Author(s):  
Alex B. Addinsall ◽  
Craig R. Wright ◽  
Sof Andrikopoulos ◽  
Chris van der Poel ◽  
Nicole Stupka
Keyword(s):  
Metabolic Disease ◽  
Endoplasmic Reticulum ◽  
Stress Responses ◽  
Cellular Stress ◽  
Metabolic Stress ◽  
Metabolic Dysfunction ◽  
Iodothyronine Deiodinase ◽  
Inflammatory Stress ◽  
Cellular Stress Responses

Chronic metabolic stress leads to cellular dysfunction, characterized by excessive reactive oxygen species, endoplasmic reticulum (ER) stress and inflammation, which has been implicated in the pathogenesis of obesity, type 2 diabetes and cardiovascular disease. The ER is gaining recognition as a key organelle in integrating cellular stress responses. ER homeostasis is tightly regulated by a complex antioxidant system, which includes the seven ER-resident selenoproteins — 15 kDa selenoprotein, type 2 iodothyronine deiodinase and selenoproteins S, N, K, M and T. Here, the findings from biochemical, cell-based and mouse studies investigating the function of ER-resident selenoproteins are reviewed. Human experimental and genetic studies are drawn upon to highlight the relevance of these selenoproteins to the pathogenesis of metabolic disease. ER-resident selenoproteins have discrete roles in the regulation of oxidative, ER and inflammatory stress responses, as well as intracellular calcium homeostasis. To date, only two of these ER-resident selenoproteins, selenoproteins S and N have been implicated in human disease. Nonetheless, the potential of all seven ER-resident selenoproteins to ameliorate metabolic dysfunction warrants further investigation.

scholarly journals CReP mediates selective translation initiation at the endoplasmic reticulum

2020 ◽  
Vol 6 (23) ◽  
pp. eaba0745 ◽  
Author(s):  
Jonathan P. Kastan ◽  
Elena Y. Dobrikova ◽  
Jeffrey D. Bryant ◽  
Matthias Gromeier
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Synthesis ◽  
Translation Initiation ◽  
Stress Responses ◽  
Spatial Organization ◽  
Acute Stress ◽  
Cell Fractionation ◽  
Local Protein Synthesis ◽  
Eif2α Phosphorylation ◽  
Selective Translation

Eukaryotic protein synthesis control at multiple levels allows for dynamic, selective responses to diverse conditions, but spatial organization of translation initiation machinery as a regulatory principle has remained largely unexplored. Here we report on a role of constitutive repressor of eIF2α phosphorylation (CReP) in translation of poliovirus and the endoplasmic reticulum (ER)–resident chaperone binding immunoglobulin protein (BiP) at the ER. Functional, proximity-dependent labeling and cell fractionation studies revealed that CReP, through binding eIF2α, anchors translation initiation machinery at the ER and enables local protein synthesis in this compartment. This ER site was protected from the suppression of cytoplasmic protein synthesis by acute stress responses, e.g., phosphorylation of eIF2α(S51) or mTOR blockade. We propose that partitioning of translation initiation machinery at the ER enables cells to maintain active translation during stress conditions associated with global protein synthesis suppression.

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