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
PATZ1 is a DNA damage-responsive transcription factor that inhibits p53 function
Nazli Keskin,Emre Deniz,Jitka Eryilmaz,Manolya Un,Tugce Batur,Tulin Ersahin,Tulin Ersahin,Rengul Cetin Atalay,Rengul Cetin Atalay,Shinya Sakaguchi,Wilfried Ellmeier,Batu Erman +11 more
TL;DR: The BTB/POZ domain transcription factor PATZ1 (MAZR), previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regulator of p53 and is documented as a novel player in the p53 pathway.
Journal ArticleDOI
Mdm2 protein expression is strongly associated with survival in malignant pleural mesothelioma.
Fabian Dominik Mairinger,Robert Fred Henry Walter,Saskia Ting,Claudia Vollbrecht,Jens Kollmeier,Sergei Griff,Thomas Hager,Thomas Mairinger,Daniel C. Christoph,Daniel C. Christoph,Dirk Theegarten,Kurt Werner Schmid,Jeremias Wohlschlaeger +12 more
TL;DR: Expression of Mdm2 is a strong prognostic factor associated with shortened overall survival in MPM and may be explained by increased MDM2 levels possibly leading to an increased ubiquitilation and proteasomal degradation of functional p53 protein.
Journal ArticleDOI
Therapeutic Efficacy of p53 Restoration in Mdm2- Overexpressing Tumors
Qin Li,Yun Zhang,Adel K. El-Naggar,Shunbin Xiong,Peirong Yang,James G. Jackson,Gilda P. Chau,Guillermina Lozano +7 more
TL;DR: It was demonstrated that elevated levels of Mdm2 and decreased levels of p53 act additively to dampen p53 activity in DNA damage response and tumor development and that restoration of wild-type p53 expression in MDM2-overexpressing angiosarcomas suppresses tumor growth.
Journal ArticleDOI
MicroRNA-552 links Wnt signaling to p53 tumor suppressor in colorectal cancer.
TL;DR: The data of this study suggest that the inhibition of miR‑552 may disconnect elevated Wnt signals from p53 suppression, providing a novel therapeutic strategy for patients with CRC with deregulated Wnt signaling.
Journal ArticleDOI
MDM2 is an important prognostic and predictive factor for platin–pemetrexed therapy in malignant pleural mesotheliomas and deregulation of P14/ARF (encoded by CDKN2A ) seems to contribute to an MDM2-driven inactivation of P53
Robert Fred Henry Walter,Fabian Dominik Mairinger,Saskia Ting,Claudia Vollbrecht,Thomas Mairinger,Dirk Theegarten,Daniel C. Christoph,Kurt Werner Schmid,Jeremias Wohlschlaeger +8 more
TL;DR: In this article, the authors used MDM2 and P14/ARF mRNA and protein expression to predict the progression-free survival (PFS) and overall survival (OS) of mesothelioma patients.
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.