Binding of Translationally Controlled Tumour Protein to the N-Terminal Domain of HDM2 Is Inhibited by Nutlin-3
| Autor: | Quah Soo. Tng, Christopher J. Brown, Loh Jiah. Tong, Farid J. Ghadessy, Chandra S. Verma, Walter Goh, Garth Funston, Siau Jia Wei, David P. Lane |
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| Přispěvatelé: | School of Biological Sciences |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Proteomics
Models Molecular Cell cycle checkpoint Cancer Treatment lcsh:Medicine Biochemistry Piperazines chemistry.chemical_compound Protein structure Molecular Cell Biology Basic Cancer Research Macromolecular Structure Analysis Signaling in Cellular Processes lcsh:Science Apoptotic Signaling Cascade Apoptotic Signaling Multidisciplinary biology Cell Death Imidazoles Tumor Protein Translationally-Controlled 1 Proto-Oncogene Proteins c-mdm2 Nutlin Signaling Cascades Cell biology Oncology Medicine Intracellular Research Article Signal Transduction Protein Binding Protein Structure Immunoprecipitation Molecular Sequence Data Protein–protein interaction Cell Line Biomarkers Tumor Humans Amino Acid Sequence Binding site Protein Interactions Biology lcsh:R Proteins Computational Biology Protein Structure Tertiary chemistry Small Molecules biology.protein Translationally controlled tumour protein lcsh:Q |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 8, p e42642 (2012) |
| ISSN: | 1932-6203 |
| Popis: | Translationally Controlled Tumour Protein (TCTP), a highly conserved protein present in all eukaryotic organisms, has a number of intracellular and extracellular functions including an anti-apoptotic role. TCTP was recently shown to interact with both p53 and HDM2, inhibiting auto-ubiquitination of the latter and thereby promoting p53 degradation. In this study, we further investigated the interaction between TCTP and HDM2, mapping the reciprocal binding sites of TCTP and HDM2. TCTP primarily interacts with the N-terminal, p53-binding region of HDM2 through its highly basic domain 2. Furthermore, we discovered that Nutlin-3, a small molecule known to promote apoptosis and cell cycle arrest by blocking binding between HDM2 and p53, has a similar inhibitory effect on the interaction of HDM2 and TCTP. This result may provide an additional explanation of how Nutlin-derived compounds currently in clinical trials function to promote apoptosis in cancer cells. Published version |
| Databáze: | OpenAIRE |
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