title: Ubiquitin: tool and target for intracellular NF-kappaB inhibitors.
abstract: The transcription factor nuclear factor-kappaB (NF-kappaB) has a pivotal role in initiating inflammation and raising an effective immune response. Because NF-kappaB activation depends on ubiquitination, cells have developed ubiquitin (Ub)-mediated strategies for inhibiting NF-kappaB activation and preventing excessive inflammation. Recent findings concerning tumor necrosis factor (TNF) receptor and toll-like receptor (TLR)-interleukin-1 (IL-1) receptor signalling pathways show that Ub can be a tool as well as a target for NF-kappaB inhibitory proteins, either by labelling specific signalling proteins for proteasome-dependent degradation or by serving as a target for specific de-ubiquitinating enzymes that prevent the formation of pertinent signalling complexes. Interfering with ubiquitination therefore seems to be a versatile means for regulating NF-kappaB activity, indicating that studies of Ub-mediated signalling might hold the key for developing new therapeutic strategies for inflammatory disease.
authors.affiliation: Unit of Molecular Signal Transduction in Inflammation, Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology (VIB) - Ghent University, Technologiepark 927, B-9052 Ghent (Zwijnaarde), Belgium.
authors.forename: Andy
authors.initials: A
authors.lastname: Wullaert
authors.forename: Karen
authors.initials: K
authors.lastname: Heyninck
authors.forename: Sophie
authors.initials: S
authors.lastname: Janssens
authors.forename: Rudi
authors.initials: R
authors.lastname: Beyaert
mesh_terms: D000818:Animals; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D051193:Toll-Like Receptors; D025801:Ubiquitin