Polyubiquitination of the neurotrophin receptor p75 directs neuronal cell survival
- 作者：Thangiah Geetha<sup>asup><sup> ; sup><sup>1sup> ; Chen Zheng<sup>asup><sup> ; sup><sup>1sup> ; Bradford Unroe<sup>asup> ; Marina Sycheva<sup>asup> ; Heidi Kluess<sup>bsup> ; Jeganathan Ramesh Babu<sup>asup><sup> ; sup><sup>jeganrb@auburn.edusup>
- 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<sup>NTRsup>) leads to p75<sup>NTRsup> polyubiquitination and its subsequent interaction with TRAF6 resulting in neuronal cell survival. However, when the binding of NGF to p75<sup>NTRsup> was blocked with p75 antiserum, p75<sup>NTRsup> polyubiquitination and neuronal cell survival were impaired. Results showed that tyrosine phosphorylation of p75<sup>NTRsup> increased the polyubiquitination of p75<sup>NTRsup> and contributed to the observed apparent neuroprotective effects. Similar to p75<sup>NTRsup> polyubiquitination, interaction of TRAF6 with p75<sup>NTRsup> 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<sup>NTRsup> mediates neuronal cell survival.