Role for the p53 homologue p73 in E2F-1-induced apoptosis.
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.
Irwin
M
M
Dana-Farber Cancer Institute and Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Marin
M C
MC
Phillips
A C
AC
Seelan
R S
RS
Smith
D I
DI
Liu
W
W
Flores
E R
ER
Tsai
K Y
KY
Jacks
T
T
Vousden
K H
KH
Kaelin
W G
WG
D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry; D025521:Tumor Suppressor Proteins
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D009687:Nuclear Proteins; D056465:Retinoblastoma-Binding Protein 1; C000606460:TP73 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D004247:DNA