C-Myc Protein-Protein and Protein-DNA Interactions: Targets for Therapeutic Intervention.
Abstract
Members of the basic-helix-loop-helix (bHLH) family of transcription factors are involved in various aspects of cell growth and differentiation, and the bHLH protein c-Myc has been implicated in breast cancer. We have determined that certain bHLH DNA binding region amino acids, which are critical for protein function but not required for high-affinity DNA binding, actually influence DNA recognition and binding conformation, and are required to maintain binding specificity. The data identify seemingly subtle effects on DNA binding that have important functional consequences, and they provide insights into how different bHLH proteins can act on different targets. The zinc finger protein TTP is induced by many different growth factors, including EGF, and is required for regulation of TNFalpha activity. We have shown that forced TTP expression drives cells to proliferate, then undergo apoptosis, and can synergize with TNFalpha in promoting apoptosis. Our data suggest that TTP is important in growth factor signaling, and that its role in TNFalpha function is likely to be complex. Efforts that are underway to identify factors that interact with TTP-related proteins are likely to allow molecular investigations of how these proteins function, and to reveal new regulatory circuits that operate during growth factor responses.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA344737
Entities
People
- T. K. Blackwell