Regulation of I Kappa B beta degradation: Similarities to and differences from I Kappa B alpha

The transcription factor NF- Kappa B (nuclear factor- Kappa B) is neutralized in nonstimulated cells through cytoplasmic retention by I Kappa B inhibitors. In mammalian cells, two major forms of I Kappa B proteins, I Kappa B alpha and I Kappa B beta , have been identified. Upon treatment with a larg...

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Bibliographic Details
Published in:The Journal of biological chemistry 1997-04, Vol.272 (15), p.9942-9949
Main Authors: Weil, R, Laurent-Winter, C, Israeel, A
Format: Article
Language:English
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Summary:The transcription factor NF- Kappa B (nuclear factor- Kappa B) is neutralized in nonstimulated cells through cytoplasmic retention by I Kappa B inhibitors. In mammalian cells, two major forms of I Kappa B proteins, I Kappa B alpha and I Kappa B beta , have been identified. Upon treatment with a large variety of inducers, I Kappa B alpha and I mu B beta are proteolytically degraded, resulting in NF- Kappa B translocation into the nucleus. Recent observations suggest that phosphorylation of serines 32 and 36 and subsequent ubiquitination of lysines 21 and 22 of I Kappa B alpha control its signal-induced degradation. In this study we provide evidence that critical residues in the NH sub(2)-terminal region of I Kappa B beta (serines 19 and 23) as well as its COOH-terminal PEST region control I Kappa B beta proteolysis. However Lys-9, the unique lysine residue in the NH sub(2)-terminal region of I Kappa B beta , is not absolutely required for its degradation. We also demonstrate that following stimulation, an underphosphorylated nondegradable form of I Kappa B beta accumulates. Surprisingly, our data suggest that unlike I Kappa B alpha , I Kappa B beta is constitutively phosphorylated on one or two of the critical NH sub(2)-terminal serine residues. Thus, phosphorylation of these sites is necessary for degradation but does not necessarily constitute the signal-induced event that targets the molecule for proteolysis.
ISSN:0021-9258
DOI:10.1074/jbc.272.15.9942