Polyubiquitination of the neurotrophin receptor p75 directs neuronal cell survival

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• 作者：Thangiah Geetha^a ; ¹ ; Chen Zheng^a ; ¹ ; Bradford Unroe^a ; Marina Sycheva^a ; Heidi Kluess^b ; Jeganathan Ramesh Babu^a ; ^{jeganrb@auburn.edu}
• 关键词：p75NTR ; p75 neurotrophin receptor ; NGF ; nerve growth factor ; Ub ; ubiquitination ; MTT ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyltetrazolium bromide ; TRAF6 ; tumor necrosis factor receptor-associated factor 6 ; DMEM ; Dulbecco&rsquo ; s modified Eagle&rsquo ; s me
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：4 May, 2012
• 卷：421
• 期：2
• 页码：286-290
• 文件大小：493 K

摘要

Specific binding of nerve growth factor (NGF) to p75 neurotrophin receptor (p75^NTR) leads to p75^NTR polyubiquitination and its subsequent interaction with TRAF6 resulting in neuronal cell survival. However, when the binding of NGF to p75^NTR was blocked with p75 antiserum, p75^NTR polyubiquitination and neuronal cell survival were impaired. Results showed that tyrosine phosphorylation of p75^NTR increased the polyubiquitination of p75^NTR and contributed to the observed apparent neuroprotective effects. Similar to p75^NTR polyubiquitination, interaction of TRAF6 with p75^NTR was NGF/tyrosine phosphorylation dependent suggesting that TRAF6 might function as an E3 ubiquitin ligase. In sum, the results show that specific binding of NGF to p75^NTR mediates neuronal cell survival.