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Binding of nerve growth factor to its p75 receptor in stressed cells induces selective IκB‐β degradation and NF‐κB nuclear translocation
Author(s) -
Cosgaya Jose Miguel,
Shooter Eric M.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00573.x
Subject(s) - nerve growth factor , chromosomal translocation , gene isoform , transcription factor , receptor , microbiology and biotechnology , tumor necrosis factor alpha , nf κb , endocrinology , cell culture , medicine , iκbα , biology , nfkb1 , chemistry , signal transduction , biochemistry , genetics , gene
Nerve growth factor (NGF) regulates the activity of the transcription factor NF‐κB (nuclear factor‐κB) through its low affinity receptor, p75. In the present study we found that NGF binding to p75 induces nuclear translocation of p65 and increases NF‐κB binding activity in a cell line overexpressing p75, but only after the cells have been subjected to a previous stress. Under physiological conditions, in the absence of stress, NGF is unable to alter p65 nuclear levels. Tumor necrosis factor‐α (TNF‐α) induces a down‐regulation of IκB‐α, ‐β and ‐ε both in physiological and in stress, i.e. serum‐free, conditions. In contrast, NGF only induces the specific degradation of IκB‐β after serum withdrawal, without affecting IκB‐α or ‐ε either in the presence or in the absence of stress. IκB‐β consists of several isoforms, whose relative abundance is regulated by serum withdrawal. NGF does not target all the IκB‐β isoforms with the same potency, being more effective in reducing the levels of the isoforms up‐regulated by serum withdrawal. TRAF‐6 is expressed at the same level under both physiological and stress conditions. These results indicate that NGF is able to induce NF‐κB nuclear translocation by a mechanism that involves specific IκB‐β degradation only after the cells have been subjected to a severe stress.