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Ring finger protein 219 regulates inflammatory responses by stabilizing sirtuin 1.

Authors
  • Hwang, Jung Seok1
  • Kim, Eunsu1
  • Hur, Jinwoo1
  • Yoon, Taek Joon2
  • Seo, Han Geuk1
  • 1 College of Sang-Huh Life Sciences, Konkuk University, Seoul, Republic of Korea. , (North Korea)
  • 2 Department of Food Science and Nutrition, Yuhan University, Bucheon-si, Republic of Korea. , (North Korea)
Type
Published Article
Journal
British Journal of Pharmacology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Oct 01, 2020
Volume
177
Issue
20
Pages
4601–4614
Identifiers
DOI: 10.1111/bph.15060
PMID: 32220064
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Ring finger protein 219 (RNF219), a protein containing the C3 HC4 -type RING-HC motif, has been identified as a binding partner of the histone deacetylase sirtuin 1 (SIRT1). To explore the functions of RNF219, we examined its possible roles in the cellular responses to inflammation. Effects of RNF219 on SIRT1 were studied in vitro using RAW264.7 cells and in male BALB/c mice, treated with LPS or IFN-γ. Western blots, RT-PCR, co-immunoprecipitation and ubiquitination assays were used, along with LC-MS/MS analysis. In vivo, survival and serum cytokines and tissue levels of RNF219 and SIRT1 were measured. Binding of RNF219 to SIRT1 inhibited degradation of SIRT1 by preventing its ubiquitination, thereby prolonging SIRT1-mediated anti-inflammatory signalling. LPS caused RNF219 deacetylation, leading to instability of RNF219 and preventing its association with SIRT1. Accordingly, the acetylation status of RNF219 is a critical determinant in its interaction with SIRT1, affecting the response to inflammatory stimuli. The deacetylase inhibitor trichostatin A, increased acetylation and stability of RNF219 and survival of mice injected with LPS, through the interaction of RNF219 with SIRT1. RNF219 is involved in a novel mechanism to stabilize SIRT1 protein by protein-protein interaction, leading to the resolution of cellular inflammation. These observations provide new insights into the function of RNF219 in modulation of cellular inflammation, and may aid and encourage the development of new anti-inflammatory drugs. © 2020 The British Pharmacological Society.

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