| First Author | Busuttil V | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 42 | Pages | 18061-6 |
| PubMed ID | 20921405 | Mgi Jnum | J:165536 |
| Mgi Id | MGI:4837612 | Doi | 10.1073/pnas.1006163107 |
| Citation | Busuttil V, et al. (2010) NF-kappaB inhibits T-cell activation-induced, p73-dependent cell death by induction of MDM2. Proc Natl Acad Sci U S A 107(42):18061-6 |
| abstractText | NF-kappaB is a key transcription factor involved in the regulation of T-cell activation and proliferation upon engagement of the T-cell receptor (TCR). T cells that lack the IkappaB kinase (IKKbeta) are unable to activate NF-kappaB, and rapidly undergo apoptosis upon activation. NF-kappaB activation following T-cell receptor engagement induces the expression of Mdm2 through interaction with NF-kappaB sites in its P1 promoter, and enforced expression of Mdm2 protected T cells deficient for NF-kappaB activation from activation-induced cell death. In T cells with intact NF-kappaB signaling, ablation or pharmacologic inhibition of Mdm2 resulted in activation-induced apoptosis. Mdm2 coprecipitates with p73 in activated T cells, and apoptosis induced by inhibition of Mdm2 was p73-dependent. Further, Bim was identified as a p73 target gene required for cell death induced by Mdm2 inhibition, and a p73-responsive element in intron 1 of Bim was characterized. Our results demonstrate a pathway for survival of activated T cells through NF-kappaB-induced Mdm2, which blocks Bim-dependent apoptosis through binding and inhibition of p73. |
