Role for the p53 homologue p73 in E2F-1-induced apoptosis.
Journal:
Nature 2000 OctAuthors:
Irwin M, Marin MC, Phillips AC, Seelan RS, Smith DI, Liu W, Flores ER, Tsai KY, Jacks T, Vousden KH, Kaelin WG
Abstract
The transcription factor E2F-1 induces both cell-cycle progression and, in certain settings, apoptosis. E2F-1 uses both p53-dependent and p53-independent pathways to kill cells. The p53-dependent pathway involves the induction by E2F-1 of the human tumour-suppressor protein p14ARF, which neutralizes HDM2 (human homologue of MDM2) and thereby stabilizes the p53 protein. Here we show that E2F-1 induces the transcription of the p53 homologue p73. Disruption of p73 function inhibited E2F-1-induced a
...[more]poptosis in p53-defective tumour cells and in p53-/- mouse embryo fibroblasts. We conclude that activation of p73 provides a means for E2F-1 to induce death in the absence of p53.[less]
Mesh Headings:
Animals, Apoptosis, Carrier Proteins, Cell Cycle Proteins, Cell Line, DNA, DNA-Binding Proteins, E2F Transcription Factors, E2F1 Transcription Factor, Gene Expression Regulation, Genes, Tumor Suppressor, Mice, Mutation, Nuclear Proteins, Protein Binding, Retinoblastoma-Binding Protein 1, Transcription Factor DP1, Transcription Factors, Transcription, Genetic, Tumor Suppressor Protein p53, Tumor Suppressor Proteins