S. Miyamoto et al., TUMOR-NECROSIS-FACTOR ALPHA-INDUCED PHOSPHORYLATION OF I-KAPPA-B-ALPHA IS A SIGNAL FOR ITS DEGRADATION BUT NOT DISSOCIATION FROM NF-KAPPA-B, Proceedings of the National Academy of Sciences of the United Statesof America, 91(26), 1994, pp. 12740-12744
Activation of the NF-kappa B/Rel family of transcription factors is re
gulated by a cytoplasmic inhibitor, I kappa B alpha, Activity of I kap
pa B alpha is in turn modulated by phosphorylation and proteolysis. It
has been postulated that phosphorylation of I kappa B alpha leads to
its dissociation from NF-kappa B, and free I kappa B alpha is targeted
for rapid degradation. However, this phosphorylation-mediated dissoci
ation event has not been demonstrated in vivo, We demonstrate that, co
ntrary to this hypothesis, phosphorylation of I kappa B alpha induced
by tumor necrosis factor alpha in HeLa cells does not induce dissociat
ion. We propose a model in which (i) induced phosphorylation of I kapp
a B alpha does not result in its dissociation from NF-kappa B, (ii) ph
osphorylation of I kappa B alpha serves as a signal for degradation, a
nd (iii) degradation of I kappa B alpha occurs while it is still compl
exed with NF-kappa B.