Regulation at multiple levels of NF-kappaB-mediated transactivation by protein acetylation.
Evidence has accumulated that deacetylation and acetylation events are implicated in the regulation of NF-kappaB transcriptional activity. Several groups have reported potentiation of NF-kappaB-mediated gene induction [by specific inducers (such as TNFalpha)], following deacetylase inhibition by trichostatin A or sodium butyrate. This potentiation reflects a complex acetylation-dependent regulation of NF-kappaB-dependent transactivation. This acetylation-dependent regulation occurs at multiple levels. First, acetylation of histones regulates the NF-kappaB-dependent gene accessibility. Second, unidentified acetylation events modulate temporally the IKK activity and subsequently the duration of NF-kappaB presence and DNA-binding in the nucleus. Third, direct acetylation of the NF-kappaB subunits p65 and p50 regulates different NF-kappaB functions, including transcriptional activation, DNA-binding affinity and IkappaBalpha assembly. Finally, acetyltransferases and deacetylases interact directly with several proteins involved in the NF-kappaB signaling pathway, including NF-kappaB itself, IkappaBalpha, IKKalpha and IKKgamma. These interactions probably allow acetylation of NF-kappaB itself, of other transcription factors and of histones associated with NF-kappaB-regulated genes. The present review discusses these recent data obtained on the role of protein acetylation in the regulation of the NF-kappaB cascade.
Institut de Biologie et de Médecine Moléculaires, Service de Chimie Biologique, Laboratoire de Virologie Moléculaire, Université Libre de Bruxelles, Rue des Profs Jeener et Brachet 12, 6041 Gosselies, Belgium.
Vincent
V
Quivy
Carine
C
Van Lint
D000107:Acetylation; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000502:physiology; D002843:Chromatin / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology; D050863:Synaptotagmin I; D050857:Synaptotagmins; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002135:Calcium-Binding Proteins; D002843:Chromatin; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009419:Nerve Tissue Proteins; D050863:Synaptotagmin I; D014409:Tumor Necrosis Factor-alpha; D050857:Synaptotagmins; D000072000:NF-KappaB Inhibitor alpha; D006655:Histone Deacetylases