NDLI: Dual Effects of IκB Kinase β-Mediated Phosphorylation on p105 Fate: SCFβ-TrCP-Dependent Degradation and SCFβ-TrCP-Independent Processing

Content Provider	PubMed Central
Author	Cohen, Shai Achbert-weiner, Hillit Ciechanover, Aaron
Copyright Year	2004
Abstract	Processing of the p105 NF-κB precursor to yield the p50 active subunit is a unique and rare case in which the ubiquitin system is involved in limited processing rather than in complete destruction of its target. The mechanisms involved in this process are largely unknown, although a glycine repeat in the middle of p105 has been identified as a processing stop signal. IκB kinase (IKK)β-mediated phosphorylation at the C-terminal domain with subsequent recruitment of the SCFβ-TrCP ubiquitin ligase leads to accelerated processing and degradation of the precursor, yet the roles that the kinase and ligase play in each of these two processes have not been elucidated. Here we demonstrate that IKKβ has two distinct functions: (i) stimulation of degradation and (ii) stimulation of processing. IKKβ-induced degradation is dependent on SCFβ-TrCP, which acts through multiple lysine residues in the IκBγ domain. In contrast, IKKβ-induced processing of p105 is β-transduction repeat-containing protein (β-TrCP) independent, as it is not affected by expression of a dominant-negative β-TrCP or following its silencing by small inhibitory RNA. Furthermore, removal of all 30 lysine residues from IκBγ results in complete inhibition of IKK-dependent degradation but has no effect on IKK-dependent processing. Yet processing still requires the activity of the ubiquitin system, as it is inhibited by dominant-negative UbcH5a. We suggest that IKKβ mediates its two distinct effects by affecting, directly and indirectly, two different E3s.
Related Links	http://dx.doi.org/10.1128/mcb.24.1.475-486.2004
Ending Page	486
Page Count	12
Starting Page	475
File Format	PDF
ISSN	02707306
e-ISSN	10985549
Journal	Molecular and Cellular Biology
Issue Number	1
Volume Number	24
Language	English
Publisher	American Society for Microbiology
Publisher Date	2004-01-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Cell Biology Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology

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