C-MYC Protein-Protein and Protein-DNA Interactions: Targets for Therapeutic Intervention

摘要

Basic-helix-loop-helix (bHLH) transcription factor proteins are involved in cell growth and differentiation, and the bHLH protein c-Myc has been implicated in breast cancer. We have determined that the sequence preference and specificity with which particular bHLH protein subclasses bind DNA are determined by binding conformations, which in turn are dictated by certain bHLH DNA binding region amino acids that are critical for protein function, but not for binding affinity. The data identify subtle effects on DNA binding that have important biological consequences, and reveal mechanisms by which different protein sub-family members can bind to different sites that share the CANNTG consensus. The zinc finger protein TTP is induced by many growth factors, and is required for regulation of TNFalpha expression.