title: Receptor proximal kinases in NF-κB signaling as potential therapeutic targets in cancer and inflammation.
abstract: Many signaling pathways leading to activation of transcription factors and gene expression are characterized by phosphorylation events mediated by specific kinases. The transcription factor NF-κB plays a key role in multiple cellular processes, including immune signaling, inflammation, development, proliferation and survival. Dysregulated NF-κB activation is associated with autoimmunity, chronic inflammation and cancer. Activation of NF-κB requires IκB kinase (IKK)α or β, the activity of which is regulated via phosphorylation by specific IKK kinases and by autophosphorylation. Receptor specificity is further obtained by the use of multiple upstream receptor proximal kinases. We review the identities of several IKK regulatory kinases as well as the proposed molecular mechanisms. In addition, we discuss the potential for therapeutic targeting of some of these kinases in the context of inflammatory diseases and cancer.
authors.affiliation: Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Lynn
authors.initials: L
authors.lastname: Verstrepen
authors.affiliation: Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. Electronic address: Rudi.Beyaert@irc.vib-UGent.be.
authors.forename: Rudi
authors.initials: R
authors.lastname: Beyaert
mesh_terms: D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D011494:Protein Kinases
keywords: 5Z-7-ozozeanol (PubChem CID: 9863776); Cancer; Fasudil (PubChem CID: 3547); IMD-0354 (PubChem CID: 5081913); Inflammation; KN-93 (PubChem CID: 5312122); KRX-0401 (PubChem CID: 148177); Kinase; MK-2206 (PubChem CID: 46930998); MLN-0415 (PubChem CID: 56603702); NF-κB; SPC-839 (PubChem CID: 9820526); Sotrastaurin (PubChem CID: 10296883); Therapy; Y27632 (PubChem CID: 448042)