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

doi:10.1038/35036614

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

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

513 Scopus citations

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 language	English (US)
Pages (from-to)	645-648
Number of pages	4
Journal	Nature
Volume	407
Issue number	6804
DOIs	https://doi.org/10.1038/35036614
State	Published - Oct 5 2000

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title = "Role for the p53 homologue p73 in E2F-1-induced apoptosis",

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.",

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

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doi = "10.1038/35036614",

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T1 - Role for the p53 homologue p73 in E2F-1-induced apoptosis

AU - Irwin, Meredith

AU - Marin, Maria Carmen

AU - Phillips, Andrew C.

AU - Seelan, Ratnam S.

AU - Smith, David I.

AU - Liu, Wanguo

AU - Flores, Elsa R.

AU - Tsai, Kenneth Y.

AU - Jacks, Tyler

AU - Vousden, Karen H.

AU - Kaelin, William G.

PY - 2000/10/5

Y1 - 2000/10/5

N2 - 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.

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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JO - Nature

JF - Nature

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ER -

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

Abstract

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