Journal ArticleDOI
Keeping p53 in check: essential and synergistic functions of Mdm2 and Mdm4.
Jean-Christophe Marine,Sarah Francoz,Marion M. Maetens,Geoffrey M. Wahl,Franck Toledo,Franck Toledo,Guillermina Lozano +6 more
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TLDR
This work presents a novel and scalable approach to gene expression engineering that allows for real-time annotation of gene expression changes in response to cancerigenicity and shows promise in finding novel and efficient treatments for cancer.Abstract:
1 Laboratory For Molecular Cancer Biology, Flanders Interuniversity Institute for Biotechnology (VIB), University of Ghent, Technologiepark, 927, Ghent B9052, Belgium 2 Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, CA 92037, USA 3 Gene Expression and Diseases Unit, Institut Pasteur, Paris, France 4 The University of Texas Graduate School of Biomedical Sciences and department of Molecular Genetics, Section of Cancer Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA * Corresponding author: J-C Marine, Laboratory For Molecular Cancer Biology, VIB, Technologiepark, 927, Ghent B-9052, Belgium. Tel: þ 32-93-313-640; Fax: þ 32-93-313-516; E-mail: chris.marine@dmbr.ugent.beread more
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Blinded by the Light: The Growing Complexity of p53
Karen H. Vousden,Carol Prives +1 more
TL;DR: Control of p53's transcriptional activity is crucial for determining which p53 response is activated, a decision that must be understood if the next generation of drugs that selectively activate or inhibit p53 are to be exploited efficiently.
Journal ArticleDOI
p53 in health and disease.
Karen H. Vousden,David P. Lane +1 more
TL;DR: It is now becoming clear that p53 can have a much broader role and can contribute to the development, life expectancy and overall fitness of an organism.
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Modes of p53 regulation.
Jan Philipp Kruse,Wei Gu +1 more
TL;DR: It is proposed that antirepression, the release of p53 from repression by factors such as Mdm2 and MdmX, is a key step in the physiological activation of p 53.
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Regulating the p53 pathway: in vitro hypotheses, in vivo veritas
Franck Toledo,Geoffrey M. Wahl +1 more
TL;DR: This Review of in vitro studies, human tumour data and recent mouse models shows that p53 post-translational modifications have modulatory roles, and MDM2 andMDM4 have more profound roles for regulating p53.
Journal ArticleDOI
Mutant p53: one name, many proteins
TL;DR: Mechanisms by which Mutant p53 exerts its cellular effects are reviewed, with a particular focus on the burgeoning mutant p53 transcriptome, and the biological and clinical consequences of mutant p 53 gain of function are discussed.
References
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MdmX Protects p53 from Mdm2-Mediated Degradation
TL;DR: It is proposed that the MdmX protein may function to maintain a nuclear pool of p53 protein in undamaged cells and is capable of associating with p53 yet is unable to facilitate nuclear export or induce p53 degradation.
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Flexible lid to the p53-binding domain of human Mdm2: implications for p53 regulation.
TL;DR: NMR studies of apo-MDM2 have found that, in addition to Mdm2 residues 25–109 that form the well ordered p53-binding domain that was observed in the p52–Mdm2 complex, MDM2 residues 16–24 form a lid that closes over the p53 -binding site.
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The tumorigenic potential and cell growth characteristics of p53-deficient cells are equivalent in the presence or absence of Mdm2
Stephen N. Jones,Arthur T. Sands,Amy R. Hancock,Hannes Vogel,Lawrence A. Donehower,Steven P. Linke,Geoffrey M. Wahl,Allan Bradley +7 more
TL;DR: Deletion of Mdm2 has no additional effect on cell proliferation, cell cycle control, or tumorigenesis when p53 is absent, and cell cycle studies indicate no difference in the ability of the two cell populations to enter S phase when treated with DNA-damaging agents or nucleotide antimetabolites.
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Rescue of Mdm4-deficient mice by Mdm2 reveals functional overlap of Mdm2 and Mdm4 in development.
TL;DR: It is demonstrated that Mdm2 can regulate both p53-mediated apoptosis and inhibition of cell growth in the absence of Mdm4 in primary cells, indicating that MDM4 has antioncogenic properties when MDM2 is overexpressed.