C-Myc Protein-Protein and Protein-DNA Interactions: Targets for Therapeutic Intervention.

摘要

Abnormalities in c-myc regulation are associated with breast carcinoma. We have begun to investigate molecular interactions that are functionally essential for c-Myc and other basic-helix-loop-helix (bHLH) proteins, both to illuminate aspects of their biology and to provide a basis for future design of therapeutics. To study bHLH dimerization, we are continuing to construct and analyze mutants in the bHLll protein MyoD. We have also expanded our investigations of how different bHLH proteins recognize different related DNA sequences. In these experiments, we are focusing on the role of basic segment residues that have been implicated in transcriptional activation, and are testing the prediction that these residues are critical for proper positioning of the DNA-bound basic regions. We have also begun a new set of experiments to investigate whether the Mastermind protein, which contains a single basic region, is a DNA-binding protein. Mastermind has been implicated as a critical element in the functioning of Notch proteins, which in turn have been implicated in mammary oncogenesis.