Proceedings of the National Academy of Sciences · 2012 · 24 citations · 46 references
Natural SciencesMolecular BiologyOncologyBiosensorsNanomaterialsNanotechnologyCancer NanomedicineCell-nanoparticle InteractionsNanomedicineNanoparticle DesignRaman SpectroscopySurface Functionalization Of NanomaterialsAggregationNanoparticle AssemblyNanoparticle Surface FunctionalizationNanoparticlesP53 MutationProtein AllosterySurface-enhanced Raman ScatteringSurface-enhanced Raman Spectroscopy
The tumor suppressor protein, p53, is either mutated or absent in >50% of cancers and is negatively regulated by the mouse double minute (MDM2) protein. Understanding and inhibition of the MDM2-p53 interaction are, therefore, critical for developing novel chemotherapeutics, which are currently limited because of a lack of appropriate study tools. We present a nanosensing approach to investigate full-length MDM2 interactions with p53, thus providing an allosteric assay for identifying binding ligands. Surface-enhanced Raman scattering (SERS)-active nanoparticles, functionalized with a p53 peptide mimic (peptide 12.1), display biologically specific aggregation following addition of MDM2. Nanoparticle assembly is competitively inhibited by the N-terminal MDM2-binding ligands peptide 12.1 and Nutlin-3. This study reports nanoparticle assembly through specific protein-peptide interactions that can be followed by SERS. We demonstrate solution-based MDM2 allosteric interaction studies that use the full-length protein.
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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 et al. · Science · 2004 · 4.7K citations
Medicine, Oncology, Pharmacology +15
Amplification of a gene encoding a p53-associated protein in human sarcomas
Jonathan D. Oliner, Kenneth W. Kinzler, Paul S. Meltzer et al. · Nature · 1992 · 2K citations · Full text