ArticleThe Journal of cell biology2007
Translation attenuation by PERK balances ER glycoprotein synthesis with lipid-linked oligosaccharide flux.
Article in The Journal of cell biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Pharmacologic Approaches for Adapting Proteostasis in the Secretory Pathway to Ameliorate Protein Conformational Diseases.Cold Spring Harbor perspectives in biology · 2020Review
- Chaperone-Mediated Autophagy Promotes Beclin1 Degradation in Persistently Infected Hepatitis C Virus Cell Culture.The American journal of pathology · 2018Article
- Activation of PERK-Nrf2 oncogenic signaling promotes Mdm2-mediated Rb degradation in persistently infected HCV culture.Scientific reports · 2017Article
- Arsenite Regulates Prolongation of Glycan Residues of Membrane Glycoprotein: A Pivotal Study via Wax Physisorption Kinetics and FTIR Imaging.International journal of molecular sciences · 2016Article
- Use of a small molecule cell cycle inhibitor to control cell growth and improve specific productivity and product quality of recombinant proteins in CHO cell cultures.Biotechnology and bioengineering · 2015Article
- N-glycan remodeling on glucagon receptor is an effector of nutrient sensing by the hexosamine biosynthesis pathway.The Journal of biological chemistry · 2014Article
- Article
- High-throughput screening identifies aclacinomycin as a radiosensitizer of EGFR-mutant non-small cell lung cancer.Translational oncology · 2013Article
- A zebrafish model of PMM2-CDG reveals altered neurogenesis and a substrate-accumulation mechanism for N-linked glycosylation deficiency.Molecular biology of the cell · 2012Article
- Life with too much polyprenol: polyprenol reductase deficiency.Molecular genetics and metabolism · 2012Article
- Chemical and biological approaches for adapting proteostasis to ameliorate protein misfolding and aggregation diseases: progress and prognosis.Cold Spring Harbor perspectives in biology · 2011Review
- Mannose-6-phosphate regulates destruction of lipid-linked oligosaccharides.Molecular biology of the cell · 2011Article
- PERK (EIF2AK3) regulates proinsulin trafficking and quality control in the secretory pathway.Diabetes · 2010Article
- Review
- Towards a therapy for phosphomannomutase 2 deficiency, the defect in CDG-Ia patients.Biochimica et biophysica acta · 2009Review
- Exogenous mannose does not raise steady state mannose-6-phosphate pools of normal or N-glycosylation-deficient human fibroblasts.Molecular genetics and metabolism · 2009Article
- Induction of incomplete autophagic response by hepatitis C virus via the unfolded protein response.Hepatology (Baltimore, Md.) · 2008Article
- Translational repression during chronic hypoxia is dependent on glucose levels.RNA (New York, N.Y.) · 2008Article
- Activation of the unfolded protein response is associated with pulmonary hypertension.Pulmonary circulationArticle
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Endoplasmic reticulum (ER) homeostasis requires transfer and subsequent processing of the glycan Glc(3)Man(9)GlcNAc(2) (G(3)M(9)Gn(2)) from the lipid-linked oligosaccharide (LLO) glucose(3)mannose(9)N-acetylglucosamine(2)-P-P-dolichol (G(3)M(9)Gn(2)-P-P-Dol) to asparaginyl residues of nascent glycoprotein precursor polypeptides. However, it is unclear how the ER is protected against dysfunction from abnormal accumulation of LLO intermediates and aberrant N-glycosylation, as occurs in certain metabolic diseases. In metazoans phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) on Ser(51) by PERK (PKR-like ER kinase), which is activated by ER stress, attenuates translation initiation. We use brief glucose deprivation to simulate LLO biosynthesis disorders, and show that attenuation of polypeptide synthesis by PERK promotes extension of LLO intermediates to G(3)M(9)Gn(2)-P-P-Dol under these substrate-limiting conditions, as well as counteract abnormal N-glycosylation. This simple mechanism requires eIF2alpha Ser(51) phosphorylation by PERK, and is mimicked by agents that stimulate cytoplasmic stress-responsive Ser(51) kinase activity. Thus, by sensing ER stress from defective glycosylation, PERK can restore ER homeostasis by balancing polypeptide synthesis with flux through the LLO pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.