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Published on: August 2, 2024
SETD7 promotes LC3B methylation and degradation in ovarian cancer
Ziwei Zhang1, Mingyang Li1, Yanan Hou1
1Department of Basic Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
Abstract:
Microtubule-associated protein 1 light chain 3 (LC3) is a key autophagy-related protein involved in regulating autophagosome formation and autophagy activity. Post-translational modifications of LC3 are necessary to modulate its function. However, LC3 protein methylation and its physiological significance have not yet been elucidated. Here, we show that SET domain containing lysine methyltransferase 7 (SETD7) interacts with LC3B, a common isoform of LC3, and methylates LC3B at lysine 51 (K51). SETD7-mediated methylation of LC3B promotes ubiquitination and degradation of LC3B, resulting in reduced autophagosome formation. Furthermore, SETD7 exerts a tumor-promotive function in ovarian cancer (OC) cells in a K51 methylation-dependent manner. Collectively, our data define a novel modification of LC3B and highlight the oncogenic effect of SETD7 via mediating LC3B methylation and degradation.
Insights
This study reveals SET domain containing lysine methyltransferase 7 (SETD7) methylates Microtubule-associated protein 1 light chain 3 B (LC3B) at K51. This methylation promotes LC3B degradation, reduces autophagosome formation, and drives ovarian cancer progression.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Microtubule-associated protein 1 light chain 3 (LC3) is crucial for autophagy.
- Post-translational modifications regulate LC3 function.
- LC3 methylation and its physiological roles remain largely unknown.
Purpose of the Study:
- To investigate the role of LC3 protein methylation.
- To identify the enzyme responsible for LC3 methylation.
- To elucidate the functional and oncogenic significance of LC3 methylation.
Main Methods:
- Co-immunoprecipitation to detect protein interactions.
- In vitro methylation assays.
- Western blotting to assess protein levels and ubiquitination.
- Cell culture and functional assays in ovarian cancer cells.
Main Results:
- SET domain containing lysine methyltransferase 7 (SETD7) directly interacts with and methylates LC3B at lysine 51 (K51).
- SETD7-mediated LC3B methylation enhances LC3B ubiquitination and degradation.
- This leads to reduced autophagosome formation.
- SETD7 promotes ovarian cancer cell proliferation in a K51 methylation-dependent manner.
Conclusions:
- LC3B K51 methylation is a novel post-translational modification.
- SETD7-induced LC3B methylation and degradation contribute to ovarian cancer progression.
- This pathway represents a potential therapeutic target in ovarian cancer.
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