The survival of antigen-stimulated T cells requires NFkappaB-mediated inhibition of p73 expression.
We have explored the interactions between the NFkappaB and Cdk-Rb-E2F pathways in controlling T cell fate following antigen stimulation. The inhibition of NFkappaB in antigen-stimulated T cells results in apoptosis but does not inhibit E2F activation and S phase entry. IkappaB-induced apoptosis coincides with the superinduction of p73 expression and activity. G1 Cdk activity is required for IkappaB-induced apoptosis and the induction of p73. Importantly, p73 deficiency rescues activated T cells from the apoptosis resulting from the inhibition of NFkappaB. Thus, Cdk2 activation sends signals for both cell cycle progression and apoptosis, the latter of which must be blocked by NFkappaB to allow for proliferation.
Wan
Yisong Y
YY
Program in Molecular Biology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
DeGregori
James
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D017209:Apoptosis; D002453:Cell Cycle; D002470:Cell Survival; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D000941:Antigens; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D018844:Cyclin-Dependent Kinases