Role for the p53 homologue p73 in E2F-1-induced apoptosis

Meredith Irwin, Maria Carmen Marin, Andrew C. Phillips, Ratnam S. Seelan, David I Smith, Wanguo Liu, Elsa R. Flores, Kenneth Y. Tsai, Tyler Jacks, Karen H. Vousden, William G. Kaelin

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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.

Original languageEnglish (US)
Pages (from-to)645-648
Number of pages4
JournalNature
Volume407
Issue number6804
DOIs
StatePublished - Oct 5 2000

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E2F1 Transcription Factor
Tumor Suppressor Protein p14ARF
Apoptosis
Cell Cycle
Embryonic Structures
Fibroblasts
Neoplasms
Proteins

ASJC Scopus subject areas

  • General

Cite this

Irwin, M., Marin, M. C., Phillips, A. C., Seelan, R. S., Smith, D. I., Liu, W., ... Kaelin, W. G. (2000). Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature, 407(6804), 645-648. https://doi.org/10.1038/35036614

Role for the p53 homologue p73 in E2F-1-induced apoptosis. / Irwin, Meredith; Marin, Maria Carmen; Phillips, Andrew C.; Seelan, Ratnam S.; Smith, David I; Liu, Wanguo; Flores, Elsa R.; Tsai, Kenneth Y.; Jacks, Tyler; Vousden, Karen H.; Kaelin, William G.

In: Nature, Vol. 407, No. 6804, 05.10.2000, p. 645-648.

Research output: Contribution to journalArticle

Irwin, M, Marin, MC, Phillips, AC, Seelan, RS, Smith, DI, Liu, W, Flores, ER, Tsai, KY, Jacks, T, Vousden, KH & Kaelin, WG 2000, 'Role for the p53 homologue p73 in E2F-1-induced apoptosis', Nature, vol. 407, no. 6804, pp. 645-648. https://doi.org/10.1038/35036614
Irwin M, Marin MC, Phillips AC, Seelan RS, Smith DI, Liu W et al. Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature. 2000 Oct 5;407(6804):645-648. https://doi.org/10.1038/35036614
Irwin, Meredith ; Marin, Maria Carmen ; Phillips, Andrew C. ; Seelan, Ratnam S. ; Smith, David I ; Liu, Wanguo ; Flores, Elsa R. ; Tsai, Kenneth Y. ; Jacks, Tyler ; Vousden, Karen H. ; Kaelin, William G. / Role for the p53 homologue p73 in E2F-1-induced apoptosis. In: Nature. 2000 ; Vol. 407, No. 6804. pp. 645-648.
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AU - Liu, Wanguo

AU - Flores, Elsa R.

AU - Tsai, Kenneth Y.

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AB - 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.

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