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Unpacking the unfolded protein response
Carolyn A Worby1, Jack E Dixon1
1Departments of Pharmacology, Cellular and Molecular Medicine, and Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Cell
|September 13, 2014
Summary
Scientists Peter Walter and Kazutoshi Mori won the Lasker Award for uncovering the molecular basis of the unfolded protein response. This crucial cellular system maintains protein health within the endoplasmic reticulum.
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- The endoplasmic reticulum (ER) is vital for protein synthesis and folding.
- Misfolded proteins accumulate in the ER during cellular stress, posing a threat to cell function.
- An adaptive cellular mechanism is required to manage ER proteostasis.
Discussion:
- The unfolded protein response (UPR) is a conserved signaling pathway that mitigates ER stress.
- UPR activation involves sensors in the ER membrane that detect misfolded proteins.
- Signaling cascades transmit stress information from the ER to the nucleus to restore homeostasis.
Key Insights:
- Peter Walter and Kazutoshi Mori elucidated the intricate molecular mechanisms governing the UPR.
- Their work identified key sensors and downstream effectors of the UPR pathway.
- These discoveries revealed how cells detect and respond to harmful misfolded proteins.
Outlook:
- Understanding the UPR is critical for developing therapies for diseases associated with protein misfolding.
- Dysregulation of the UPR is implicated in neurodegenerative disorders, metabolic diseases, and cancer.
- Targeting the UPR offers potential therapeutic strategies for a range of human pathologies.
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