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Published on: June 3, 2018
ZDHHC18-YTHDF2 axis suppresses USP13 to drive cardiac hypertrophy
Hanping Qi1, Lina Ba2, Ruixuan Wang2
1Department of Pharmacology, Harbin Medical University, Daqing Campus, Daqing, 163319, Heilongjiang, China; Key Laboratory of Frigid Zone Exercise Health Research and Translation in Heilongjiang Province, Daqing, 163319, Heilongjiang, China.
Deubiquitinating enzyme 13 (USP13) suppresses cardiac hypertrophy by stabilizing sorting nexin 13 (SNX13), which protects against ferroptosis. This pathway offers a novel therapeutic target for heart failure.
Area of Science:
- Cardiovascular Biology
- Molecular Mechanisms of Disease
- Biochemistry
Background:
- Cardiac hypertrophy is a pathological response to stress, often leading to heart failure.
- Identifying novel therapeutic targets is crucial for managing cardiac hypertrophy.
Purpose of the Study:
- To investigate the role of deubiquitinating enzyme 13 (USP13) in cardiac hypertrophy.
- To elucidate the molecular mechanisms underlying USP13's function in this condition.
Main Methods:
- Integrated transcriptomic and proteomic analysis.
- Functional experiments involving USP13 overexpression in a cardiac hypertrophy model.
- Mechanistic studies on protein interactions and post-translational modifications.
Main Results:
- USP13 was significantly downregulated in cardiac hypertrophy.
- USP13 overexpression ameliorated cardiac dysfunction and cardiomyocyte hypertrophy.
- USP13 stabilized SNX13, promoting Nrf2 nuclear accumulation and upregulating ferroptosis regulators (SLC7A11, GPX4).
- YTHDF2-mediated degradation of USP13 mRNA was identified, regulated by ZDHHC18-dependent palmitoylation.
Conclusions:
- USP13 acts as a suppressor of cardiac hypertrophy by modulating the SNX13/Nrf2/ferroptosis axis.
- The ZDHHC18/YTHDF2/USP13 signaling pathway represents a potential therapeutic target for cardiac hypertrophy.
