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
More filters
Journal ArticleDOI
Blinded by the Light: The Growing Complexity of p53
Karen H. Vousden,Carol Prives +1 more
TL;DR: Control of p53's transcriptional activity is crucial for determining which p53 response is activated, a decision that must be understood if the next generation of drugs that selectively activate or inhibit p53 are to be exploited efficiently.
Journal ArticleDOI
p53 in health and disease.
Karen H. Vousden,David P. Lane +1 more
TL;DR: It is now becoming clear that p53 can have a much broader role and can contribute to the development, life expectancy and overall fitness of an organism.
Journal ArticleDOI
Modes of p53 regulation.
Jan Philipp Kruse,Wei Gu +1 more
TL;DR: It is proposed that antirepression, the release of p53 from repression by factors such as Mdm2 and MdmX, is a key step in the physiological activation of p 53.
Journal ArticleDOI
Regulating the p53 pathway: in vitro hypotheses, in vivo veritas
Franck Toledo,Geoffrey M. Wahl +1 more
TL;DR: This Review of in vitro studies, human tumour data and recent mouse models shows that p53 post-translational modifications have modulatory roles, and MDM2 andMDM4 have more profound roles for regulating p53.
Journal ArticleDOI
Mutant p53: one name, many proteins
TL;DR: Mechanisms by which Mutant p53 exerts its cellular effects are reviewed, with a particular focus on the burgeoning mutant p53 transcriptome, and the biological and clinical consequences of mutant p 53 gain of function are discussed.
References
More filters
Journal ArticleDOI
Pirh2, a p53-Induced Ubiquitin-Protein Ligase, Promotes p53 Degradation
Roger P. Leng,Yunping Lin,Weili Ma,Hong Wu,Bénédicte Lemmers,Bénédicte Lemmers,Stephen Chung,John M. Parant,Guillermina Lozano,Razqallah Hakem,Razqallah Hakem,Samuel Benchimol +11 more
TL;DR: Pirh2, a gene regulated by p53 that encodes a RING-H2 domain-containing protein with intrinsic ubiquitin-protein ligase activity, is described and it is proposed that Pirh2 is involved in the negative regulation of p53 function through physical interaction and ubiquit in-mediated proteolysis.
Journal ArticleDOI
The ubiquitin ligase COP1 is a critical negative regulator of p53.
David Dornan,Ingrid E. Wertz,Ingrid E. Wertz,Harumi Shimizu,David Arnott,Gretchen Frantz,Patrick Dowd,Karen O'Rourke,Hartmut Koeppen,Vishva M. Dixit +9 more
TL;DR: COP1 is a critical negative regulator of p53 and represents a new pathway for maintaining p53 at low levels in unstressed cells and is identified as a p53-inducible gene.
Journal Article
In Vivo Ubiquitination and Proteasome-mediated Degradation of p53
TL;DR: In this study, inhibitors of the 26S proteasome have been used to further explore the role of ubiquitin proteolysis in regulating p53 turnover and indicate that ubiquitIn-p53 conjugates were detected in untreated as well as gamma-irradiated cells, indicating that Ubiquitin-dependent proteolytic plays a role in the normal turnover of p53.
Journal ArticleDOI
Mdm2-Mediated NEDD8 Conjugation of p53 Inhibits Its Transcriptional Activity
TL;DR: The role for MDM2 as an E3 ligase is expanded, providing evidence that Mdm2 is a common component of the ubiquitin and NEDD8 conjugation pathway and indicating the diverse mechanisms by which E3ligases can control the function of substrate proteins.
Journal ArticleDOI
ARF-BP1/Mule Is a Critical Mediator of the ARF Tumor Suppressor
TL;DR: It is revealed that ARF-BP1 is a critical mediator of both the p53-independent and p 53-dependent tumor suppressor functions of ARF, and may serve as a potential target for therapeutic intervention in tumors regardless of p53 status.