Regulation of IκBβ Degradation

The transcription factor NF-κB (nuclear factor-κB) is neutralized in nonstimulated cells through cytoplasmic retention by IκB inhibitors. In mammalian cells, two major forms of IκB proteins, IκBα and IκBβ, have been identified. Upon treatment with a large variety of inducers, IκBα and IκB...

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Bibliographic Details
Published in:The Journal of biological chemistry 1997-04, Vol.272 (15), p.9942
Main Authors: Robert Weil, Christine Laurent-Winter, Alain Israël
Format: Article
Language:English
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Summary:The transcription factor NF-κB (nuclear factor-κB) is neutralized in nonstimulated cells through cytoplasmic retention by IκB inhibitors. In mammalian cells, two major forms of IκB proteins, IκBα and IκBβ, have been identified. Upon treatment with a large variety of inducers, IκBα and IκBβ are proteolytically degraded, resulting in NF-κB translocation into the nucleus. Recent observations suggest that phosphorylation of serines 32 and 36 and subsequent ubiquitination of lysines 21 and 22 of IκBα control its signal-induced degradation. In this study we provide evidence that critical residues in the NH 2 -terminal region of IκBβ (serines 19 and 23) as well as its COOH-terminal PEST region control IκBβ proteolysis. However Lys-9, the unique lysine residue in the NH 2 -terminal region of IκBβ, is not absolutely required for its degradation. We also demonstrate that following stimulation, an underphosphorylated nondegradable form of IκBβ accumulates. Surprisingly, our data suggest that unlike IκBα, IκBβ is constitutively phosphorylated on one or two of the critical NH 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
1083-351X
DOI:10.1074/jbc.272.15.9942