Different enzymatic activities recruitment by specific domains of TIF2 are involved in NF-kappaB transactivation

• Published in: Medicina (Buenos Aires) Vol. 64; no. 2; pp. 135 - 138
• Main Authors: Nojek, Ignacio M, Werbajh, Santiago E, Colo, Georgina P, Rubio, Fernanda M, Franco, Lorena D, Nahmod, Victor E, Costas, Monica A
• Format: Journal Article
• Language: Spanish
• Published: Argentina 2004
• Subjects: Cell Nucleus - metabolism; Cytoplasm - metabolism; Enzyme Activation; Humans; NF-kappa B - metabolism; Nuclear Receptor Coactivator 2; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Transcription Factors - physiology; Transcriptional Activation
• ISSN: 0025-7680

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.