The helix-loop-helix (HLH) family of transcription factors regulate cellular growth and differentiation. The goal of this proposal is to understand on a molecular level the origins of binding affinity between HLH domains. These domains mediate protein-protein contacts among HLH transcription factors, altering their DNA-binding specificity and thus regulating transcription. Domains from the HLH transcription factors controlling myogenesis, MyoD, E47, and Id, will be used as a model system. The structures of the Id homo-oligomer as well as the hetero-oligomers will be studied crystallographically, their binding energies will be measured, and hypotheses for their relative binding affinities will be tested through mutagenesis. From these results, we will generate an algorithm to predict the pairing of HLH sequences. Developing a set of rules for HLH domain interactions will enable us to design specific probes for the expression of transcription factors in vivo. Ultimately this information may form the basis for new strategies to restore the normal function of HLH transcription factors that cause uncontrolled proliferation and de-differentiation in tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA069747-02
Application #
2443235
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1997-06-17
Project End
Budget Start
1997-06-17
Budget End
1998-06-16
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704