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Updated: Jun 21, 2025
10:36
Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
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An HSF1-JMJD6-HSP feedback circuit promotes cell adaptation to proteotoxic stress
Milad J Alasady1,2,3, Martina Koeva4,5,6, Seesha R Takagishi1,2,3
1Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.
Summary
Heat Shock Factor 1 (HSF1) activates Jumonji domain-containing protein 6 (JMJD6) expression. JMJD6 then enhances HSF1 activity, creating a feedback loop crucial for cellular adaptation to proteotoxic stress and maintaining protein homeostasis.
Area of Science:
- Molecular Biology
- Cellular Stress Response
Background:
- Heat Shock Factor 1 (HSF1) is the primary regulator of the heat-shock response (HSR).
- The HSR is vital for maintaining protein homeostasis (proteostasis) under cellular stress.
- Understanding HSF1 regulation is key to comprehending cellular adaptive mechanisms.
Purpose of the Study:
- To identify novel mediators of HSF1 activity in the heat-shock response.
- To elucidate the regulatory role of Jumonji domain-containing protein 6 (JMJD6) in proteostasis.
- To characterize the feedback mechanism between HSF1 and JMJD6.
Main Methods:
- Genome-wide RNA interference (RNAi) library screening.
- Utilized a heat-shock response (HSR) reporter system.
- Investigated protein-protein interactions and transcriptional regulation.
Main Results:
- Identified JMJD6 as a critical mediator of HSF1 activity.
- Demonstrated that JMJD6 is a transcriptional target of HSF1, forming a positive feedback loop.
- Showed that JMJD6 modulates HSP70 monomethylation, disrupting repressive complexes and enhancing HSF1 activation.
Conclusions:
- JMJD6 is intricately integrated into the proteostasis network.
- JMJD6 plays a crucial role in cellular adaptation to proteotoxic stress.
- The HSF1-JMJD6 feedback circuit is essential for robust proteostasis maintenance.
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