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Stability of Homologue of Slimb F-box Protein Is Regulated by Availability of Its Substrate
- Source :
- Journal of Biological Chemistry. 279:11074-11080
- Publication Year :
- 2004
- Publisher :
- Elsevier BV, 2004.
-
Abstract
- The homologue of Slimb (HOS) F-box protein is a receptor of the Skp1-Cullin1-F-box protein (SCF(HOS)) E3 ubiquitin ligase, which mediates ubiquitination and degradation of beta-catenin and the inhibitor of NFkappaB, IkappaB. We found that HOS itself is an unstable protein that undergoes ubiquitination and degradation in a 26 S proteasome-dependent manner. A HOS mutant lacking the F-box that is deficient in binding to the core SCF components underwent ubiquitination less efficiently and was more stable than the wild type protein. Furthermore, ubiquitination and degradation of HOS was impaired in ts41 cells, in which the activities of Cullin-based ligases were decreased because the NEDD8 pathway was abrogated. Whereas HOS was directly ubiquitinated within the SCF(HOS) complex in vitro, the addition of phosphorylated IkappaBalpha inhibited this ubiquitination. Increasing cellular levels of HOS substrate (phosphorylated IkappaBalpha) by activating IkappaB kinase inhibited HOS ubiquitination and led to stabilization of HOS, indicating that interaction between HOS and its substrate might protect HOS from proteolysis. Taken together, our data suggest that proteolysis of HOS depends on its interaction with active components of the SCF complex and that HOS stability is regulated by a bound substrate. These findings may define a mechanism for maintaining activities of specific SCF complexes based on availability of a particular substrate.
- Subjects :
- Proteasome Endopeptidase Complex
IκB kinase
Biochemistry
NEDD8
F-box protein
Cell Line
Substrate Specificity
SCF complex
Ubiquitin
Multienzyme Complexes
Humans
Molecular Biology
DNA Primers
Base Sequence
biology
Hydrolysis
Proteins
Cell Biology
Ubiquitin ligase
Cysteine Endopeptidases
IκBα
Mutation
biology.protein
Cullin
DNA Damage
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 279
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....f5bcb8504da5c0e262247c3e749c6a4d