Journal ArticleDOI
Role for the p53 homologue p73 in E2F-1-induced apoptosis
Meredith S. Irwin,Maria C. Marin,Andrew C. Phillips,Ratnam S. Seelan,David I. Smith,Wanguo Liu,Elsa R. Flores,Kenneth Y. Tsai,Tyler Jacks,Tyler Jacks,Karen H. Vousden,William G. Kaelin,William G. Kaelin +12 more
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TLDR
It is concluded that activation of p73 provides a means for E2F-1 to induce death in the absence of p53, and the transcription of the p53 homologue p73 is induced.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 cells1,2,3,4,5,6,7,8. 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 protein9. 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.read more
Citations
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Journal ArticleDOI
Live or let die: the cell's response to p53
Karen H. Vousden,Xin Lu +1 more
TL;DR: Understanding the complex mechanisms that regulate whether or not a cell dies in response to p53 will ultimately contribute to the development of therapeutic strategies to repair the apoptotic p53 response in cancers.
Journal ArticleDOI
Control of apoptosis by p53.
Jordan S. Fridman,Scott W. Lowe +1 more
TL;DR: The current understanding of p53 illustrates how apoptosis can be integrated into a larger tumor suppressor network controlled by different signals, environmental factors, and cell type.
Journal ArticleDOI
Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome.
Kenneth P. Olive,David A. Tuveson,Zachary C. Ruhe,Bob Yin,Nicholas A. Willis,Roderick T. Bronson,Denise Crowley,Tyler Jacks,Tyler Jacks +8 more
TL;DR: It is demonstrated that point mutant p53 alleles expressed under physiological control have enhanced oncogenic potential beyond the simple loss of p53 function.
Journal ArticleDOI
Sibling rivalry in the E2F family.
TL;DR: The E2F transcription factor family determines whether or not a cell will divide by controlling the expression of key cell-cycle regulators as mentioned in this paper, and individual E2Fs can be divided into distinct subgroups that act in direct opposition to one another.
Journal ArticleDOI
The INK4a / ARF network in tumour suppression
TL;DR: A complex signalling network that interconnects the activities of RB and p53 monitors oncogenic stimuli to provide a cell-autonomous mode of tumour surveillance.
References
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Journal ArticleDOI
The regulation of E2F by pRB-family proteins
TL;DR: The rapid growth in the size of the E2F literature hides the fact that several fundamental questions have not been fully answered, and the second section of this review details five unresolved issues that have been highlighted by recent publications.
Journal ArticleDOI
p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities.
Annie Yang,Mourad Kaghad,Yunmei Wang,Emily Gillett,Mark D. Fleming,Mark D. Fleming,Mark D. Fleming,Volker Dötsch,Nancy C. Andrews,Nancy C. Andrews,Daniel Caput,Frank McKeon +11 more
TL;DR: The cloning of p63, a gene at chromosome 3q27-29 that bears strong homology to the tumor suppressor p53 and to the related gene, p73, is described and the possibility of physiological interactions among members of the p53 family is suggested.
Journal ArticleDOI
Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers.
Mourad Kaghad,Helene Bonnet,Annie Yang,Laurent Creancier,Jean-Christophe Biscan,A. Valent,Adrian Minty,Pascale Chalon,Jean-Michel Lelias,Xavier Dumont,Pascual Ferrara,Frank McKeon,Daniel Caput +12 more
TL;DR: The demonstration that p73 is monoallelically expressed supports the notion that it is a candidate gene in neuroblastoma and proposes that the disregulation of p73 contributes to tumorigenesis and that p53-related proteins operate in a network of developmental and cell cycle controls.
Journal ArticleDOI
p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours
Annie Yang,Nancy Walker,Roderick T. Bronson,Mourad Kaghad,Mariëtte A. Oosterwegel,Jacques Bonnin,Christine Vagner,Helene Bonnet,Pieter Dikkes,Arlene H. Sharpe,Frank McKeon,Daniel Caput +11 more
TL;DR: It is shown that mice functionally deficient for all p73 isoforms exhibit profound defects, including hippocampal dysgenesis, hydrocephalus, chronic infections and inflammation, as well as abnormalities in pheromone sensory pathways, and there is a marked divergence in the physiological functions of the p53 family members.
Journal ArticleDOI
p14ARF links the tumour suppressors RB and p53.
Stewart Bates,Andrew C. Phillips,Paula A. Clark,Francesca J. Stott,Gordon Peters,Robert L. Ludwig,Karen H. Vousden +6 more
TL;DR: It is shown that E2F-1 directly activates expression of the human tumour-suppressor protein p14ARF (the mouse homologue is called p19ARF), which binds to the MDM2-p53 complex and prevents p53 degradation,.