NF-κB activation by Reactive Oxygen Species- Fifteen yea.docVIP

NF-κB activation by Reactive Oxygen Species: Fifteen years later Geoffrey Gloire, Sylvie Legrand-Poels and Jacques Piette Center for Biomedical Integrated Genoproteomics (CBIG), Virology and Immunology Unit, University of Liège, 4000 Liège, Belgium Address for correspondence: Dr Jacques Piette CBIG/GIGA Virology and Immunology Unit Institute of Pathology B23, B-4000 Liège Belgium Email: jpiette@ulg.ac.be Tel: + 32 4 366 24 42 Fax: + 32 4 366 99 33 Key Words: NF-κB, Reactive Oxygen Species, Cellular signalling, Cytokines, LPS Abbreviations: ROS?: Reactive Oxygen Species; SOD?: superoxide dismutase; PEST?: proline, glutamate, serine, threonine; p56Lck?: lymphocyte specific tyrosine kinase; ZAP70?: zeta-chain (TCR) associated protein kinase?; Syk?: spleen tyrosine kinase?; SHIP-1: SH2-containing inositol 5-phosphatase 1?; PKD: protein kinase D?; Abl: abelson murine leukemia viral?; PKCδ?: protein kinase Cδ?; NAC?: N-acetyl-cysteine?; PDTC?: pyrrolidie-9-dithocarbamate?; GSH?: reduced gluthation?; MyD88?: myeloid differentiation marker?88?; TAK1: transforming growth factor-β-activated kinase?; JNK: c-Jun N-terminal kinase?; BHA: butylated hydroxyanisole?; DMSO: dimethylsulfoxide?; ASK1: apoptosis signal-regulating kinase1. ABSTRACT The transcription factor NF-κB plays a major role in coordinating innate and adaptative immunity, cellular proliferation, apoptosis and development. Since the discovery in 1991 that NF-?B may be activated by H2O2, several laboratories have put a considerable effort into dissecting the molecular mechanisms underlying this activation. Whereas early studies revealed an atypical mechanism of activation, leading to IκBα Y42 phosphorylation independently of IκB Kinase (IKK), recent findings suggest that H2O2 activate NF-κB mainly through the classical IKK-dependent pathway. The molecular mechanisms leading to IKK activation are, however, cell-type specific, and will be presented here. In this review, we also describe the effect of other ROS (HO