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 apoptosis 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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Apoptosis*
-
Carrier Proteins*
-
Cell Cycle Proteins*
-
Cell Line
-
DNA / metabolism
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / physiology*
-
E2F Transcription Factors
-
E2F1 Transcription Factor
-
Gene Expression Regulation
-
Genes, Tumor Suppressor
-
Mice
-
Mutation
-
Nuclear Proteins / genetics
-
Nuclear Proteins / physiology*
-
Protein Binding
-
Retinoblastoma-Binding Protein 1
-
Transcription Factor DP1
-
Transcription Factors / physiology*
-
Transcription, Genetic
-
Tumor Protein p73
-
Tumor Suppressor Protein p53 / chemistry
-
Tumor Suppressor Proteins
Substances
-
Arid4a protein, mouse
-
Carrier Proteins
-
Cell Cycle Proteins
-
DNA-Binding Proteins
-
E2F Transcription Factors
-
E2F1 Transcription Factor
-
E2f1 protein, mouse
-
Nuclear Proteins
-
Retinoblastoma-Binding Protein 1
-
TP73 protein, human
-
Transcription Factor DP1
-
Transcription Factors
-
Trp73 protein, mouse
-
Tumor Protein p73
-
Tumor Suppressor Protein p53
-
Tumor Suppressor Proteins
-
DNA