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
Reads0
Chats0
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
More filters
Journal ArticleDOI
The Mdm2–p53 relationship evolves: Mdm2 swings both ways as an oncogene and a tumor suppressor
TL;DR: Growing evidence argues for p53-independent effects, as well as the remarkable possibility that Mdm2 has tumor suppressor functions in the appropriate context, which is proving to be a key player in human cancer in its own right, and thus an important target for therapeutic intervention.
Journal ArticleDOI
p53 at a glance
TL;DR: The role of the p53 protein in cancer has been studied intensively as mentioned in this paper, and p53 is a crucial tumor suppressor, long recognized to suppress cancer through the induction of cell-cycle-arrest or apoptosis programs in response to a plethora of different threats.
Journal ArticleDOI
Transcription-independent p53 apoptosis: an alternative route to death.
TL;DR: This review focuses on the mechanisms, regulation and physiological roles of transcription-independent p53 activities and highlights recent findings suggesting that the utilisation of these activities provides a promising alternative strategy for p53-based cancer therapy.
Journal ArticleDOI
The tumor suppressor p53: from structures to drug discovery.
TL;DR: Key structural aspects of p53 function and its inactivation by oncogenic mutations are discussed, including targeting mutant-specific lesions on the surface of destabilized cancer mutants with small molecules and selective inhibition of p 53's degradative pathways.
Journal ArticleDOI
Mdm2-mediated ubiquitylation: p53 and beyond
TL;DR: Advances in Mdm2-mediated regulation of p53 and how the physical and functional interactions between these two proteins are regulated are evaluated and their potential implications for the development of new cancer therapeutic strategies are reviewed.
References
More filters
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.