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Adapting Secretory Proteostasis and Function Through the Unfolded Protein Response
Madeline Y Wong1, Andrew S DiChiara1, Patreece H Suen1
1Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA, 02139-4307, USA.
Current Topics in Microbiology and Immunology
|September 21, 2017
Summary
The unfolded protein response (UPR) manages protein folding in the endoplasmic reticulum (ER) and impacts cell functions beyond stress. Modulating the UPR shows therapeutic potential for protein misfolding diseases.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- The endoplasmic reticulum (ER) faces protein folding challenges.
- The unfolded protein response (UPR) is an ER-localized protective mechanism.
- UPR involves signal transducers IRE1, PERK, and ATF6.
Purpose of the Study:
- Review advances in UPR research.
- Highlight UPR's role beyond proteotoxic stress.
- Discuss therapeutic potential of UPR modulation.
Main Methods:
- Chemical genetic methods and small molecule modulators.
- Perturbing UPR activity for studying proteostasis.
- Reviewing recent scientific literature.
Main Results:
- UPR induces gene networks to alleviate protein misfolding.
- UPR influences cell differentiation, development, and pathogen response.
- UPR modulation offers therapeutic avenues for protein misfolding diseases.
Conclusions:
- UPR is crucial for secretory pathway proteostasis.
- Targeting ER proteostasis nodes downstream of UPR is promising.
- UPR is a fundamental driver in physiology and pathology.
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