Molecular Modeling of Interactions Regulating the Activity of the p53 Protein

Division Of Basic Sciences - Nci

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Abstract

This project focuses on revealing the structural basis for the functional molecular interactions of the p53 antitumor protein. P53 is a central transcription factor that enacts cell cycle arrest and/or apoptosis in response to DNA damage and other cellular stresses. While existing at low levels in normal cells, the protein is stabilized and accumulates by post-translational modification of the sequence. Furthermore, the specific biochemical pathway subsequently stimulated by p53 is programmed by the particular pattern of chemical modification. In increasing our understanding of the structural biology of cancer, this work reveals the atomic details of new molecular targets for therapeutic drug development.