Wyatt Technology Demonstrates SEC-MALS Capabilities for Studying
Interactions of Tumor Suppressor p53 with S100 Proteins
The p53 tumor suppressor gene prevents cancer by regulating the cell cycle, activating DNA repair proteins and initiating apoptosis. However, when the p53 gene is mutated, it can no longer serve its tumor suppressor role and instead leads to cancer growth. Research has demonstrated that p53 is mutated in more than 50% of human cancers, with mutations mapping mainly to the DNAbinding core domain. At its Laboratory for Molecular Biology (LMB), the MRC Centre for Protein Engineering undertakes research in an attempt to provide understanding of the thermodynamic basis for the interactions of p53 with DNA and other proteins, as well as the effects of mutation on these interactions. The aim is to develop short peptides able to rescue p53 mutants.
The S100 family is a group of dimeric, calciumbinding proteins, which have been found to be overexpressed in several types of cancer. S100 proteins bind to the Cterminal region of p53, which encompasses a tetramerization domain. Part of the research at the LMB is to investigate how S100 proteins bind to p53 in its different oligomeric states, using monomeric and dimeric p53 mutants. The p53 variants have a large fraction of intrinsically disordered structure and do not elute according to globular protein standards in SEC. In response, Wyatt Technology's static MALS has been chosen as the ideal detection technology to study the complex formation of S100 proteins and p53 by determining the molecular weight of the complexes independently of protein standards.
The studies of the complex formation of p53 and S100 proteins by Wyatt's SEC-MALS instrumentation have helped to understand how S100 proteins influence the oligomerization of p53. Based on these results and in vivo studies, a binding model has been established where S100 proteins can activate tetrameric p53 while inhibiting p53 activity binding to the monomer by shifting the tetramerization equilibrium.
To find out more about the capabilities of Wyatt Technology's SEC and MALS instruments or to obtain a copy of the new application note, please visit www.wyatt.com or email email@example.com
Based in Santa Barbara, California, Wyatt Technology is the world's leading provider of instruments for absolute macromolecular characterization. With over 40 years' experience developing multiangle light scattering detectors, working with customers in the biotechnology, chemical, petrochemical, pharmaceutical, academic and government arenas, Wyatt prides itself on its entrepreneurial spirit, and the uniqueness of its offerings. The Company's groundbreaking technology and uncompromising levels of customer care make Wyatt the global hallmark in its field. For more information, please visit www.wyatt.com
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