title: Polyubiquitination of the neurotrophin receptor p75 directs neuronal cell survival.
abstract: 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.
authors.affiliation: Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL 36849, USA.
authors.forename: Thangiah
authors.initials: T
authors.lastname: Geetha
authors.forename: Chen
authors.initials: C
authors.lastname: Zheng
authors.forename: Bradford
authors.initials: B
authors.lastname: Unroe
authors.forename: Marina
authors.initials: M
authors.lastname: Sycheva
authors.forename: Heidi
authors.initials: H
authors.lastname: Kluess
authors.forename: Jeganathan Ramesh
authors.initials: JR
authors.lastname: Babu
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D020800:Receptor, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D019138:Antibodies, Blocking; D020800:Receptor, Nerve Growth Factor; D048029:TNF Receptor-Associated Factor 6; D014443:Tyrosine; D020932:Nerve Growth Factor