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Biochem Biophys Res Commun. 2012 May 4;421(2):286-90. doi: 10.1016/j.bbrc.2012.04.001. Epub 2012 Apr 7.

Polyubiquitination of the neurotrophin receptor p75 directs neuronal cell survival.

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Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL 36849, USA.


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.

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