The Ubiquitin-Proteasome Degradation Of Neuropathy Target Esterase Is Regulated By Ara54

• 作 者: Ding-XinLong;Ying-JianSun;Ping-AnChang;RuiChen;Yi-JunWu;
• 机 构: Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects an
• 出 处: 中国毒理学会生化与分子毒理专业委员会学术会议暨环境内分泌干扰物的毒理学研究新技术新方法研讨会
• 发表日期: 2014年期

　　As an endoplasmic reticulum membrane-associated phospholipase B, neuropathy target esterase (NTE) is essential for embryonic and nervous system development.However, little is currently known about the regulation of NTE at the protein level.We elucidate for the first time that NTE is modified not only by autophagy but also by ubiquitination and the regulatory domain of NTE is essential for its ubiquitin-proteasome degradation.In addition, we demonstrate that androgen receptor-associated protein 54 (ARA54) interacts directly with NTE.Over-expression of ARA54 down-regulates the protein level of NTE.On the contrary, knockdown of ARA54 by RNA interference inhibits the degradation of NTE.Furthermore, over-expression of ARA54 mutant without ubiquitin-ligase does not affect protein level.These findings indicate that ARA54 acts as ubiquitin-ligase to regulate the ubiquitin-proteasome degradation of NTE and suggests there is a novel mechanism for regulating protein levels of NTE.