Tumor necrosis factor alpha-induced phosphorylation of I kappa B alpha is a signal for its degradation but not dissociation from NF-kappa B - PubMed (original) (raw)

Tumor necrosis factor alpha-induced phosphorylation of I kappa B alpha is a signal for its degradation but not dissociation from NF-kappa B

S Miyamoto et al. Proc Natl Acad Sci U S A. 1994.

Abstract

Activation of the NF-kappa B/Rel family of transcription factors is regulated by a cytoplasmic inhibitor, I kappa B alpha. Activity of I kappa 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 dissociation event has not been demonstrated in vivo. We demonstrate that, contrary to this hypothesis, phosphorylation of I kappa B alpha induced by tumor necrosis factor alpha in HeLa cells does not induce dissociation. We propose a model in which (i) induced phosphorylation of I kappa B alpha does not result in its dissociation from NF-kappa B, (ii) phosphorylation of I kappa B alpha serves as a signal for degradation, and (iii) degradation of I kappa B alpha occurs while it is still complexed with NF-kappa B.

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References

1. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4333-7 - PubMed
1. Semin Cell Biol. 1990 Dec;1(6):433-40 - PubMed
1. Mol Biol Cell. 1992 Dec;3(12):1339-52 - PubMed
1. Int Rev Cytol. 1993;143:1-62 - PubMed
1. Science. 1993 Mar 26;259(5103):1912-5 - PubMed

Tumor necrosis factor alpha-induced phosphorylation of I kappa B alpha is a signal for its degradation but not dissociation from NF-kappa B - PubMed (original) (raw)