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
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
Citations
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New insights into p53 activation
Christopher L Brooks,Wei Gu +1 more
TL;DR: Evidence suggests that the in vivo functions of p53 seem to balance the cell-fate choice with the type and severity of damage that occurs, and the concept of antirepression, or inhibition of factors that normally keep p53 at bay, may help explain the physiological mechanisms for p53 activation.
Journal ArticleDOI
Comprehensive Mapping of p53 Pathway Alterations Reveals an Apparent Role for Both SNP309 and MDM2 Amplification in Sarcomagenesis
Moriko Ito,Louise Barys,Terence O'reilly,Sophie Young,Bella O. Gorbatcheva,John Monahan,Sabine Zumstein-Mecker,Peter F. M. Choong,Ian C. Dickinson,Philip J. Crowe,Christine Hemmings,Jayesh Desai,David Thomas,Joanna Hergovich Lisztwan +13 more
TL;DR: A strong association of malignancy with TP53 mutation, or MDM2 amplification and the presence of a G allele in SNP309 is observed, especially in lipoma versus liposarcoma, which emphasizes the critical role of p53 inactivation in sarcomagenesis.
Journal ArticleDOI
Cop1 constitutively regulates c-Jun protein stability and functions as a tumor suppressor in mice.
Domenico Migliorini,Sven Bogaerts,Dieter Defever,Rajesh Vyas,Geertrui Denecker,Enrico Radaelli,Aleksandra Zwolinska,Aleksandra Zwolinska,Vanessa Depaepe,Tino Hochepied,William C. Skarnes,Jean-Christophe Marine,Jean-Christophe Marine +12 more
TL;DR: Cop1 is a tumor suppressor that functions, at least in part, by antagonizing c-Jun oncogenic activity, and the data strongly argue against the use of Cop1-inhibitory drugs for cancer therapy.
Journal ArticleDOI
Targeting mutant p53 for cancer therapy: direct and indirect strategies.
Jiahao Hu,Jiasheng Cao,Jiasheng Cao,Win Topatana,Win Topatana,Sarun Juengpanich,Shijie Li,Bin Zhang,Jiliang Shen,Liuxin Cai,Xiujun Cai,Mingyu Chen,Mingyu Chen +12 more
TL;DR: A review of treatments for cancers with mutant p53 that focus on directly targeting mutant P53, restoring wild-type functions, and exploiting synthetic lethal interactions with mutantP53 is presented in this paper.
Journal ArticleDOI
Genetics and epigenetics of human retinoblastoma.
TL;DR: This review highlights the genetic and epigenetics changes in retinoblastoma that have been reported, with special emphasis on recent whole-genome sequencing and epigenetic analyses that have identified novel candidate genes as potential therapeutic targets.
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.