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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Journal ArticleDOI
p53 Regulation by Ubiquitin
Christopher L. Brooks,Wei Gu +1 more
TL;DR: This review highlights the recent advances in the knowledge of ubiquitin and the p53 pathway.
Journal ArticleDOI
Molecular pathways: targeting Mdm2 and Mdm4 in cancer therapy.
Qin Li,Guillermina Lozano +1 more
TL;DR: Given that Mdm2 and Mdm4 inhibit p53 activities to promote tumor development, small molecules and peptides were developed to abrogate the inhibition of p53 by Mdm proteins.
Journal ArticleDOI
p53, Stem Cells, and Reprogramming: Tumor Suppression beyond Guarding the Genome
TL;DR: Recent findings supporting the connection between p53 loss and the emergence of tumor cells bearing functional and molecular similarities to stem cells are discussed.
Journal ArticleDOI
RING Domain–Mediated Interaction Is a Requirement for MDM2's E3 Ligase Activity
TL;DR: Disruption of the binding between MDM2 and MDMX resulted in a marked increase in both abundance and activity of p53, emphasizing the functional importance of this heterocomplex in p53 control.
Journal ArticleDOI
Ribosomal protein S3: A multi-functional protein that interacts with both p53 and MDM2 through its KH domain.
Sridevi Yadavilli,Lindsey D. Mayo,Maureen Higgins,Sonia Lain,Sonia Lain,Vijay Hegde,Walter A. Deutsch +6 more
TL;DR: DNA pull-down assays using a 7,8-dihydro-8-oxoguanine duplex oligonucleotide as a substrate found that RPS3 acted as a scaffold for the additional binding of MDM2 and p53, suggesting that R PS3 interacts with important proteins involved in maintaining genomic integrity.
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.
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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.
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.