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Ring finger protein 219 regulates inflammatory responses by stabilizing sirtuin 1
Jung Seok Hwang1, Eunsu Kim1, Jinwoo Hur1
1College of Sang-Huh Life Sciences, Konkuk University, Seoul, Republic of Korea.
British Journal of Pharmacology
|March 29, 2020
Summary
Ring finger protein 219 (RNF219) stabilizes sirtuin 1 (SIRT1) by preventing its degradation, thereby resolving inflammation. RNF219 acetylation controls this interaction, offering potential for new anti-inflammatory drug development.
Area of Science:
- Cellular Biology
- Molecular Mechanisms of Inflammation
- Protein Interactions
Background:
- Ring finger protein 219 (RNF219) is a protein with a C3HC4-type RING-HC motif.
- RNF219 has been identified as a binding partner of histone deacetylase sirtuin 1 (SIRT1).
Purpose of the Study:
- To investigate the functional roles of RNF219 in cellular responses to inflammation.
- To elucidate the interaction between RNF219 and SIRT1 in the context of inflammatory signaling.
Main Methods:
- In vitro studies using RAW264.7 cells and in vivo studies in male BALB/c mice.
- Techniques included Western blots, RT-PCR, co-immunoprecipitation, ubiquitination assays, and LC-MS/MS analysis.
- Measurements involved survival rates, serum cytokines, and tissue levels of RNF219 and SIRT1.
Main Results:
- RNF219 binding to SIRT1 inhibits SIRT1 ubiquitination and degradation, prolonging anti-inflammatory signaling.
- RNF219 deacetylation by lipopolysaccharide (LPS) leads to instability and dissociation from SIRT1.
- Acetylation status of RNF219 critically determines its interaction with SIRT1 and inflammatory response.
- Trichostatin A (a deacetylase inhibitor) increased RNF219 acetylation, stability, and mouse survival following LPS injection.
Conclusions:
- RNF219 stabilizes SIRT1 via protein-protein interaction, promoting the resolution of cellular inflammation.
- The acetylation of RNF219 is a key regulator of its interaction with SIRT1 and the subsequent inflammatory response.
- These findings offer novel insights into RNF219's role in inflammation and suggest potential therapeutic strategies for anti-inflammatory drug development.
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