Binding of nerve growth factor to its p75 receptor in stressed cells induces selective IκB‐β degradation and NF‐κB nuclear translocation

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Abstract
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.