Accession Number:

ADA371161

Title:

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

Descriptive Note:

Annual rept. 1 Sep 97-31 Aug 98

Corporate Author:

CENTER FOR BLOOD RESEARCH BOSTON MA

Personal Author(s):

Report Date:

1998-09-01

Pagination or Media Count:

30.0

Abstract:

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. We have shown that continuous expression of TTP or the related proteins TIS11b and TIS11d induces apoptosis and affects growth regulatory pathways. Like c-Myc, TTP also sensitizes cells to apoptosis induced by TNFalpha. Our data suggest that TTP is important in growth factor signaling, and that its role in TNFalpha function is likely to be complex. We have determined that these proteins interact with 14-3-3 proteins, which are involved in multiple signaling pathways, and are screening for additional TTPTIS11 co-factors.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE