Control of IκB-α Proteolysis by Site-Specific, Signal-Induced Phosphorylation

Keith Brown(National Institutes of Health), Susan M. Gerstberger(National Institutes of Health), Louise Carlson(National Institutes of Health), Guido Franzoso(National Institutes of Health), Ulrich Siebenlist(National Institutes of Health)
Science
March 10, 1995
10.1126/science.7878466
Cited by 1,438

Abstract

I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal-induced phosphorylation or degradation, and NF-kappa B could not be activated. These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B.

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