[Different enzymatic activities recruitment by specific domains of TIF2 are involved in NF-kappaB transactivation].
We have previously shown that nuclear receptor coactivator overexpression significantly enhanced NF-kappaB activity in a dose response manner. We studied the mechanism by which TIF2 regulates NF-kappaB activity. We determined that: 1) the p38 specific inhibitor reduces 50% NF-kappaB transcriptional activity, even in cells that overexpress distinct TIF2 deletions; 2) there is a physical interaction between TIF2 and p38 and RelA determined through in vitro translated protein binding assays; 3) TIF2 is a p38 substrate; 4) there is a physical interaction between TIF2 and IKK in TNF-alpha 20 ng/ml stimulated or not HEK 293 cell protein extract, and IkappaB only in basal conditions, determined by binding pull down assays. This NF-kappaB complex regulates its activity and targets gene expression in a determined physiologic context depending on the coactivator complex content.
Nojek
Ignacio M
IM
Instituto de Investigaciones Médicas Alfredo Lanari, Buenos Aires, Argentina.
Werbajh
Santiago E
SE
Colo
Georgina P
GP
Rubio
Fernanda M
FM
Franco
Lorena D
LD
Nahmod
Victor E
VE
Costas
Monica A
MA
D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D051958:Nuclear Receptor Coactivator 2; D010766:Phosphorylation; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
C498001:NCOA2 protein, human; D016328:NF-kappa B; D051958:Nuclear Receptor Coactivator 2; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases