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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Escape from p53-mediated tumor surveillance in neuroblastoma: switching off the
TL;DR: In this paper, the authors review the mechanisms for evasion of p53-mediated growth control and conclude that deregulation of the p14ARF-MDM2-p53 axis seems to be the principal mode of inactivation in neuroblastoma.
Journal ArticleDOI
Nutlins and Ionizing Radiation in Cancer Therapy
TL;DR: The first results obtained by using Nutlins alone or in combination with other therapeutic agents on primary tumour cells, in vitro cell lines or tumour xenografts are reported and the most recent advances in the understanding of the molecular mechanisms underlining ionizing radiation cytotoxicity and resistance are presented.
Journal ArticleDOI
Decision making of the p53 network: Death by integration
TL;DR: An integrated mathematical model is developed that embraces three key modules of the p53 network: p53 core regulation, p 53-induced cell cycle arrest and p53-dependent apoptosis initiation, and reveals that different aspects of the nuclear p53 dynamic profile are being used to differentially regulate the pro-survival and thePro-death modules.
Journal ArticleDOI
Structure and Function of p53-DNA Complexes with Inactivation and Rescue Mutations: A Molecular Dynamics Simulation Study
Balu Kamaraj,Annemie Bogaerts +1 more
TL;DR: The structural and functional consequence of p53 proteins upon DNA-contact mutations and rescue mutations and the underlying mechanisms at the atomic level are elucidated by means of molecular dynamics simulations and the docking approach is applied.
Journal ArticleDOI
miR-10a overexpression is associated with NPM1 mutations and MDM4 downregulation in intermediate-risk acute myeloid leukemia
Dmitriy Ovcharenko,Friedrich Stölzel,David M. Poitz,Fernando A. Fierro,Markus Schaich,Andreas Neubauer,Kevin Kelnar,Timothy Davison,Carsten Müller-Tidow,Christian Thiede,Martin Bornhäuser,Gerhard Ehninger,David F.M. Brown,Thomas Illmer +13 more
TL;DR: In this article, microarray analysis of miRNAs in bone marrow samples from AML (IR) patients with NPM1 mutations and healthy donors was performed to detect differential expression patterns.
References
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Journal ArticleDOI
WAF1, a potential mediator of p53 tumor suppression
Wafik S. El-Deiry,Takashi Tokino,Victor E. Velculescu,Daniel B. Levy,Ramon Parsons,Jeffrey M. Trent,D Lin,W. Edward Mercer,Kenneth W. Kinzler,Bert Vogelstein +9 more
TL;DR: A gene is identified, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line and that could be an important mediator of p53-dependent tumor growth suppression.
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In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.
Lyubomir T. Vassilev,Binh Thanh Vu,Bradford Graves,Daisy Carvajal,Frank John Podlaski,Zoran Filipovic,Norman Kong,Ursula Kammlott,Christine Lukacs,Christian Klein,Nader Fotouhi,Liu Emily Aijun +11 more
TL;DR: In this article, the authors identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts.
Journal ArticleDOI
Mdm2 promotes the rapid degradation of p53
TL;DR: It is proposed that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal.
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Regulation of p53 stability by Mdm2
TL;DR: It is shown that interaction with Mdm2 can also result in a large reduction in p53 protein levels through enhanced proteasome-dependent degradation, which may contribute to the maintenance of low p53 concentrations in normal cells.
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Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53
TL;DR: The data suggest that the MDM2 protein, which is induced by p53, functions as a ubiquitin ligase, E3, in human papillomavirus‐uninfected cells which do not have E6 protein.