Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation.
Nuclear factor-kappaB (NF-kappaB) is a transcription factor that has crucial roles in inflammation, immunity, cell proliferation and apoptosis. Activation of NF-kappaB mainly occurs via IkappaB kinase (IKK)-mediated phosphorylation of inhibitory molecules, including IkappaBalpha. Optimal induction of NF-kappaB target genes also requires phosphorylation of NF-kappaB proteins, such as p65, within their transactivation domain by a variety of kinases in response to distinct stimuli. Whether, and how, phosphorylation modulates the function of other NF-kappaB and IkappaB proteins, such as B-cell lymphoma 3, remains unclear. The identification and characterization of all the kinases known to phosphorylate NF-kappaB and IkappaB proteins are described here. Because deregulation of NF-kappaB and IkappaB phosphorylations is a hallmark of chronic inflammatory diseases and cancer, newly designed drugs targeting these constitutively activated signalling pathways represent promising therapeutic tools.
Viatour
Patrick
P
Laboratory of Medical Chemistry and Human Genetics, CHU, Sart-Tilman, Center for Biomedical Integrated Genoproteomics, University of Liege, Belgium.
Merville
Marie-Paule
MP
Bours
Vincent
V
Chariot
Alain
A
D000818:Animals; D015195:Drug Design; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D051996:Transcription Factor RelA
D020672:I-kappa B Proteins; D016328:NF-kappa B; D051996:Transcription Factor RelA