FUNCTION OF A DUAL SPECIFICITY TRANSCRIPTION FACTOR

Summary

Principal Investigator: Peter Hurlin
Abstract: DESCRIPTION (adapted from the applicant's desciption): The Myc family proteins play fundamental roles in controlling cell proliferation, and frequently contribute to oncogenesis. The biological activities of Myc proteins require heterodimerization with Max, which functions as an obligate partner for DNA-binding and transcriptional activities. Max fulfills a similar role in mediating the transcriptional and biological activities of the Myc-related proteins Mad 1-4, Mnt, and Mga. Thus, Myc proteins are thought to function as a network of Max-interacting proteins that regulate overlapping sets of target genes and biological processes. This project aims to understand the molecular and biological functions of the Mga protein and how these impinge on Myc function. The Mga protein contains a Myc-like basic-helix-loop-helix-leucine zipper (bHLHZip) domain and interacts with Max, and is of particular interest because it contains a second highly conserved DNA-binding domain called the T-domain. Proteins with a T-domain motif, such as Brachyury, regulate inductive events that govern formation of many organs and appendages during embryonic development and are implicated in various human birth defects. Mutagenesis and transcription assays will be used to test the hypothesis that Mga functions as a dual-specificity transcription factor that regulates both Myc:Max and Brachyury target genes. The potential regulatory roles imparted by Mga-interacting proteins, including a putative corepressor, will also be investigated. Finally, gene targeting in the mouse will be used to study the biological activities of Mga and the individual roles of its bHLHZip domain and T-domain.
Funding Period: 2000-07-01 - 2005-06-30
more information: NIH RePORT

Top Publications

  1. pmc Mnt-Max to Myc-Max complex switching regulates cell cycle entry
    William Walker
    Shriners Hospitals for Children, Portland, OR 97201, USA
    J Cell Biol 169:405-13. 2005

Scientific Experts

  • Peter Hurlin
  • William Walker
  • Anthony Wynshaw-Boris
  • Zi Qiang Zhou
  • Sara Ota

Detail Information

Publications1

  1. pmc Mnt-Max to Myc-Max complex switching regulates cell cycle entry
    William Walker
    Shriners Hospitals for Children, Portland, OR 97201, USA
    J Cell Biol 169:405-13. 2005
    ..These results demonstrate that Mnt-Myc antagonism plays a fundamental role in regulating cell cycle entry and proliferation...