IL-17 receptor signaling: ubiquitin gets in on the act.
Engagement of the interleukin-17 (IL-17) receptor complex triggers activation of the transcription factor nuclear factor kappaB (NF-kappaB). A wide array of signaling molecules can contribute to the activation of NF-kappaB, but a number of common themes link the receptors engaged to activate it with the translocation of the active complex to the nucleus; among these is a clear role for ubiquitination. Ubiquitination is essential to the degradation of the inhibitor of NF-kappaB (IkappaB) subunits, which otherwise retain the inactive NF-kappaB complex in the cytosol. However, additional roles for ubiquitination in the assembly of signaling complexes and in enzyme activation are underappreciated aspects of NF-kappaB induction pathways. These roles require a form of ubiquitination biochemically distinct from that which targets proteins for degradation. The identification of Act1, an adaptor protein of the IL-17 receptor, as an E3 ubiquitin ligase capable of initiating this modification provides an impressive connection between the IL-17 receptor complex and pathways that activate NF-kappaB.
Levin
Steven D
SD
Department of Immunology, ZymoGenetics Inc., Seattle, WA 98102, USA. levins@zgi.com
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*
D020381:Interleukin-17; D016328:NF-kappa B; D025801:Ubiquitin