The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Signal-induced ubiquitination of Ikappa Balpha by the F-box protein Slimb/beta -TrCP
Open accessAbstract
Signal-induced phosphorylation of IkappaBalpha targets this inhibitor of NF-kappaB for ubiquitination and subsequent degradation, thus allowing NF-kappaB to enter the nucleus to turn on its target genes. We report here the identification of an IkappaB-ubiquitin (Ub) ligase complex containing the F-box/WD40-repeat protein, beta-TrCP, a vertebrate homolog of Drosophila Slimb. beta-TrCP binds to IkappaBalpha only when the latter is specifically phosphorylated by an IkappaB kinase complex. Moreover, immunopurified beta-TrCP ubiquitinates phosphorylated IkappaBalpha at specific lysines in the presence of Ub-activating (E1) and -conjugating (Ubch5) enzymes. A beta-TrCP mutant lacking the F-box inhibits the signal-induced degradation of IkappaBalpha and subsequent activation of NF-kappaB-dependent transcription. Furthermore, Drosophila embryos deficient in slimb fail to activate twist and snail, two genes known to be regulated by the NF-kappaB homolog, Dorsal. These biochemical and genetic data strongly suggest that Slimb/beta-TrCP is the specificity determinant for the signal-induced ubiquitination of IkappaBalpha.
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Citations
Cites
A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein
Chau, V., Tobias, J. W., Bachmair, A., Marriott, D., Ecker, D. J., Gonda, D. K., & Varshavsky, A. (1989) · Science · doi:10.1126/science.2538923 · Cited by 1,535
Cited by
Phosphorylation meets ubiquitination: the control of NF-κB activity
Karin, M., & Ben-Neriah, Y. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.621 · Cited by 4,766
Hayden, M. S., & Ghosh, S. (2004) · Genes & Development · doi:10.1101/gad.1228704 · Cited by 3,842
Deng, L., Wang, C., Spencer, E., Yang, L., Braun, A., You, J., Slaughter, C., Pickart, C., & Chen, Z. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00126-4 · Cited by 1,872
Self-citationNF-κB, the first quarter-century: remarkable progress and outstanding questions
Hayden, M. S., & Ghosh, S. (2012) · Genes & Development · doi:10.1101/gad.183434.111 · Cited by 1,693
SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27
Carrano, A. C., Eytan, E., Hershko, A., & Pagano, M. (1999) · Nature Cell Biology · doi:10.1038/12013 · Cited by 1,543
Metadata
- Authors
- Spencer, E., Jiang, J., & Chen, Z. J.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1999-02-01
- Volume
- 13
- Issue
- 3
- Pages
- 284-294
- ISSN
- 0890-9369 (ISSN-L)
- OpenAlex
- W2132570074
- Cited by
- 431
- References
- 1
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Spencer, E., Jiang, J., & Chen, Z. J. (1999). Signal-induced ubiquitination of Ikappa Balpha by the F-box protein Slimb/beta -TrCP. Genes & Development. https://doi.org/10.1101/gad.13.3.284
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