SMYD2‐mediated TRAF2 methylation promotes the NF‐κB signaling pathways in inflammatory diseases

Abstract Background The methylation of lysine residues has been involved in the multiple biological and diseases processes. Recently, some particular non‐histone proteins have been elucidated to be methylated by SMYD2, a SET and MYND domain protein with lysine methyltransferase activity. Methods SMY...

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Autores principales:	Weijun Wu, Jinghuan Wang, Chenxi Xiao, Zhenghua Su, Haibi Su, Wen Zhong, Jianchun Mao, Xinhua Liu, Yi Zhun Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	inflammatory diseases NF‐κB SMYD2 TRAF2 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4e01a827b07c465d9d02ee7c8fd565da
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spelling	oai:doaj.org-article:4e01a827b07c465d9d02ee7c8fd565da2021-11-30T07:25:38ZSMYD2‐mediated TRAF2 methylation promotes the NF‐κB signaling pathways in inflammatory diseases2001-132610.1002/ctm2.591https://doaj.org/article/4e01a827b07c465d9d02ee7c8fd565da2021-11-01T00:00:00Zhttps://doi.org/10.1002/ctm2.591https://doaj.org/toc/2001-1326Abstract Background The methylation of lysine residues has been involved in the multiple biological and diseases processes. Recently, some particular non‐histone proteins have been elucidated to be methylated by SMYD2, a SET and MYND domain protein with lysine methyltransferase activity. Methods SMYD2 was evaluated in synovial tissue and cells derived from rheumatoid arthritis patients. We confirmed TRAF2 could be methylated by SMYD2 using Mass spectrometry, pull‐down, immunoprecipitation, methyltransferase assay, ubiquitination assay, luciferase reporter assays, and western blot analyses. Using loss‐ and gain‐of function studies, we explored the biological functions of SMYD2 in vitro and in vivo. Using acute and chronic inflammation with different mice models to determine the impact of SMYD2. Results Here, we first time confirmed that the cytoplasmic protein TRAF2 as the kernel node for NF‐κB signaling pathway could be methylated by SMYD2. SMYD2‐mediated TRAF2 methylation contributed to the durative sensitization of NF‐κB signaling transduction through restraining its own proteolysis and enhancing the activity. In addition, we found knocking down of SMYD2 has different degrees of mitigation in acute and chronic inflammation mice models. Furthermore, as the lysine‐specific demethylase, LSD1 could resist methylation on TRAF2 induced by SMYD2. Conclusions Our data uncovered an unprecedented cytoplasmic protein network that employed methylation of TRAF2 for the maintenance of NF‐κB activation during inflammatory diseases.Weijun WuJinghuan WangChenxi XiaoZhenghua SuHaibi SuWen ZhongJianchun MaoXinhua LiuYi Zhun ZhuWileyarticleinflammatory diseasesNF‐κBSMYD2TRAF2Medicine (General)R5-920ENClinical and Translational Medicine, Vol 11, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	inflammatory diseases NF‐κB SMYD2 TRAF2 Medicine (General) R5-920
spellingShingle	inflammatory diseases NF‐κB SMYD2 TRAF2 Medicine (General) R5-920 Weijun Wu Jinghuan Wang Chenxi Xiao Zhenghua Su Haibi Su Wen Zhong Jianchun Mao Xinhua Liu Yi Zhun Zhu SMYD2‐mediated TRAF2 methylation promotes the NF‐κB signaling pathways in inflammatory diseases
description	Abstract Background The methylation of lysine residues has been involved in the multiple biological and diseases processes. Recently, some particular non‐histone proteins have been elucidated to be methylated by SMYD2, a SET and MYND domain protein with lysine methyltransferase activity. Methods SMYD2 was evaluated in synovial tissue and cells derived from rheumatoid arthritis patients. We confirmed TRAF2 could be methylated by SMYD2 using Mass spectrometry, pull‐down, immunoprecipitation, methyltransferase assay, ubiquitination assay, luciferase reporter assays, and western blot analyses. Using loss‐ and gain‐of function studies, we explored the biological functions of SMYD2 in vitro and in vivo. Using acute and chronic inflammation with different mice models to determine the impact of SMYD2. Results Here, we first time confirmed that the cytoplasmic protein TRAF2 as the kernel node for NF‐κB signaling pathway could be methylated by SMYD2. SMYD2‐mediated TRAF2 methylation contributed to the durative sensitization of NF‐κB signaling transduction through restraining its own proteolysis and enhancing the activity. In addition, we found knocking down of SMYD2 has different degrees of mitigation in acute and chronic inflammation mice models. Furthermore, as the lysine‐specific demethylase, LSD1 could resist methylation on TRAF2 induced by SMYD2. Conclusions Our data uncovered an unprecedented cytoplasmic protein network that employed methylation of TRAF2 for the maintenance of NF‐κB activation during inflammatory diseases.
format	article
author	Weijun Wu Jinghuan Wang Chenxi Xiao Zhenghua Su Haibi Su Wen Zhong Jianchun Mao Xinhua Liu Yi Zhun Zhu
author_facet	Weijun Wu Jinghuan Wang Chenxi Xiao Zhenghua Su Haibi Su Wen Zhong Jianchun Mao Xinhua Liu Yi Zhun Zhu
author_sort	Weijun Wu
title	SMYD2‐mediated TRAF2 methylation promotes the NF‐κB signaling pathways in inflammatory diseases
title_short	SMYD2‐mediated TRAF2 methylation promotes the NF‐κB signaling pathways in inflammatory diseases
title_full	SMYD2‐mediated TRAF2 methylation promotes the NF‐κB signaling pathways in inflammatory diseases
title_fullStr	SMYD2‐mediated TRAF2 methylation promotes the NF‐κB signaling pathways in inflammatory diseases
title_full_unstemmed	SMYD2‐mediated TRAF2 methylation promotes the NF‐κB signaling pathways in inflammatory diseases
title_sort	smyd2‐mediated traf2 methylation promotes the nf‐κb signaling pathways in inflammatory diseases
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/4e01a827b07c465d9d02ee7c8fd565da
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SMYD2‐mediated TRAF2 methylation promotes the NF‐κB signaling pathways in inflammatory diseases

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