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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Dysregulation of Mdm2 and Mdm4 alternative splicing underlies motor neuron death in spinal muscular atrophy.
Meaghan Van Alstyne,Christian M. Simon,S. Pablo Sardi,Lamya S. Shihabuddin,George Z. Mentis,Livio Pellizzoni +5 more
TL;DR: It is revealed that loss of SMN-dependent regulation of Mdm2 and Mdm4 alternative splicing underlies p53-mediated death of motor neurons in SMA, establishing a causal link between snRNP dysfunction and neurodegeneration.
Journal ArticleDOI
Gambogic acid triggers DNA damage signaling that induces p53/p21Waf1/CIP1 activation through the ATR-Chk1 pathway.
TL;DR: An important role is shown of the DNA damage response mediated by ATR-Chk1 in p53/p21(Waf/CIP1) activation and downstream G2/M arrest during GA treatment, and the sensitivity to caffeine enhanced the cytotoxicity of GA as well.
Journal ArticleDOI
The p53-mediated cytotoxicity of photodynamic therapy of cancer: recent advances.
Joanna Zawacka-Pankau,Justyna Krachulec,Ireneusz Grulkowski,Krzysztof P. Bielawski,Galina Selivanova +4 more
TL;DR: The available evidence on the role of p53 in PDT is described and it is suggested that the p53 tumor suppressor protein might play a significant role in porphyrin-PDT-mediated cell death by direct interaction with the drug which leads to its accumulation and induction of p 53-dependent cell death both in the dark and upon irradiation.
Journal ArticleDOI
The MDM2 gene family.
TL;DR: Evidence is presented that COP1, Pirh2, and MSL2 evolved independently of MDM2 and MDM4, and it is shown, through structure homology models of invertebrate MDM RING domains, that MDM 2 is more evolutionarily conserved than MDM 4.
Journal ArticleDOI
Direct and Propagated Effects of Small Molecules on Protein–Protein Interaction Networks
TL;DR: In this article, the authors highlight developments that have opened the door to potent chemical modulators for protein-protein interactions (PPIs) and discuss how interfering with one PPI can propagate changes through the broader web of interactions.
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.
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.