What question did this study set out to answer?

To determine whether the endoplasmic reticulum stress-activated kinase PERK is required for eIF2alpha phosphorylation, translational attenuation, and cell survival during the unfolded protein response.

May 1, 2000Molecular CellOpen Access

Perk Is Essential for Translational Regulation and Cell Survival during the Unfolded Protein Response

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Authors

HHHeather P. HardingUniversity of Cambridge YZYuhong ZhangNingbo University ABAnne BertolottiMRC Laboratory of Molecular Biology

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Implication

Laboratory study reveals that mutating PERK impairs translational shutdown and survival in stressed cells, indicating that PERK is essential for endoplasmic reticulum stress adaptation.

Key Points

To determine whether the endoplasmic reticulum stress-activated kinase PERK is required for eIF2alpha phosphorylation, translational attenuation, and cell survival during the unfolded protein response.
Mutated the gene encoding the ER stress-activated eIF2alpha kinase PERK in cell models exposed to ER stress caused by accumulation of malfolded proteins.
Assessed eIF2alpha phosphorylation, rates of protein synthesis, and cellular survival in wild-type versus mutant cells, including rescue experiments with the protein synthesis inhibitor cycloheximide.
PERK mutation completely abolished eIF2alpha phosphorylation in response to malfolded ER proteins, resulting in abnormally elevated protein synthesis and heightened ER stress.
Mutant cells exhibited markedly impaired survival under ER stress conditions, an impairment that was ameliorated by pharmacological inhibition of protein synthesis via cycloheximide.

Cite This Study

Harding et al. (2000) studied this question.

synapsesocial.com/papers/6aa2083201abe00586ef9f47 https://doi.org/10.1016/s1097-2765(00)80330-5

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Implication

Laboratory study reveals that mutating PERK impairs translational shutdown and survival in stressed cells, indicating that PERK is essential for endoplasmic reticulum stress adaptation.

Perk Is Essential for Translational Regulation and Cell Survival during the Unfolded Protein Response

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Implication

Key Points

Cite This Study

Perk Is Essential for Translational Regulation and Cell Survival during the Unfolded Protein Response

Discussion

Member takes

Implication

Key Points

Cite This Study

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