Journal article
Emerging complexity of protein ubiquitination in the NF-κB pathway
Genes & cancer, Vol.1(7), pp.735-747
07/01/2010
DOI: 10.1177/1947601910382900
PMCID: PMC2990976
PMID: 21113390
Abstract
Members of the nuclear factor-κB (NF-κB) family of transcription factors play critical roles in regulating the expression of genes whose products are involved in inflammation, the immune response, cell proliferation, and the suppression of both death receptor- and stress-induced apoptosis. Abnormal NF-κB activation has been observed in various inflammatory diseases and many types of cancers. Gene knockout studies have clearly demonstrated that most of the physiologically relevant stimuli that activate NF-κB converge on inhibitor of κB kinase (IKK). Although the mechanism by which IKK activates NF-κB is well established, the upstream signaling mechanisms-those that underlie IKK activation by IKK kinases (IKK-Ks)-are not yet fully understood. The current belief is that members of the TNF receptor-associated factor (TRAF) family function as ubiquitin E3 ligases that catalyze non-canonical polyubiquitination of adaptor proteins, and that the ubiquitinated adaptor proteins in turn serve as platforms to recruit IKK and IKK-Ks, facilitating IKK activation through proximity-mediated phosphorylation. This review will focus on the most recent findings relating to the role of TRAFs-mediated protein ubiquitination in regulating IKK activation, and highlight the newly emerging complexity of protein ubiquitination in receptor-induced NF-κB activation.
Details
- Title: Subtitle
- Emerging complexity of protein ubiquitination in the NF-κB pathway
- Creators
- Hasem Habelhah - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Genes & cancer, Vol.1(7), pp.735-747
- Publisher
- United States
- DOI
- 10.1177/1947601910382900
- PMID
- 21113390
- PMCID
- PMC2990976
- ISSN
- 1947-6019
- eISSN
- 1947-6027
- Grant note
- R01 CA138475-02 / NCI NIH HHS R01 CA078419 / NCI NIH HHS R01 CA138475 / NCI NIH HHS
- Language
- English
- Date published
- 07/01/2010
- Academic Unit
- Pathology
- Record Identifier
- 9984046914202771
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