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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MDM4 (MDMX) localizes at the mitochondria and facilitates the p53-mediated intrinsic-apoptotic pathway
Francesca Mancini,Francesca Mancini,Giusy Di Conza,Giusy Di Conza,Marsha Pellegrino,Cinzia Rinaldo,Andrea Prodosmo,Simona Giglio,Simona Giglio,Igea D'Agnano,Fulvio Florenzano,Lara Felicioni,Fiamma Buttitta,Antonio Marchetti,Ada Sacchi,Alfredo Pontecorvi,Silvia Soddu,Fabiola Moretti +17 more
TL;DR: It is shown that MDM4 stably localizes at the mitochondria, in which it facilitates mitochondrial localization of p53 phosphorylated at Ser46 (p53Ser46P) and promotes binding between p53Ser 46P and BCL2, release of cytochrome C and apoptosis.
Journal ArticleDOI
Increased radioresistance and accelerated B cell lymphomas in mice with Mdmx mutations that prevent modifications by DNA-damage-activated kinases.
TL;DR: Data demonstrate that Mdmx downregulation is crucial for effective p53-mediated radiation responses and tumor suppression in vivo.
Journal ArticleDOI
Mdmx enhances p53 ubiquitination by altering the substrate preference of the Mdm2 ubiquitin ligase.
TL;DR: It is shown that Ubiquitin physically interacts with P53 by pull down, and the chiral stationary phase model shows good chiral recognition ability towards P53.
Journal ArticleDOI
Huntington Disease as a Neurodevelopmental Disorder and Early Signs of the Disease in Stem Cells
TL;DR: The early molecular pathogenesis of HD in pluripotent and neural stem cells, with respect to the neurodevelopmental aspects of HD, is discussed.
Journal ArticleDOI
Analysis of MDM2 and MDM4 Single Nucleotide Polymorphisms, mRNA Splicing and Protein Expression in Retinoblastoma
Justina McEvoy,Anatoly Ulyanov,Rachel C. Brennan,Gang Wu,Stanley Pounds,Jinghui Zhang,Michael A. Dyer,Michael A. Dyer,Michael A. Dyer +8 more
TL;DR: The authors found that MDM4 is the major p53 antagonist expressed in retinoblastoma and in the developing human retina and also discovered that the protein steady state levels are much higher in retinal cancer than in human fetal retinae.
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.
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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.