Structural Studies of the PU.1 Transcription Factor.
Annual rept. 1 Sep 94-31 Aug 95,
LA JOLLA CANCER RESEARCH FOUNDATION CA
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Transcription factors bind to target DNA sequences and regulate important metabolic functions such as cell growth, development and differentiation. There is great interest in characterizing these regulatory proteins, especially when their role is linked to oncogenesis. The PU.1 transcription factor is a member of the ets gene family and is identical to the spl.1 oncogene. The PU.1 factor and other ets molecules have been implicated in oncogenic processes such as the development of erythroid leukemia. Recent studies suggest that ets proteins contribute to tumorigenesis in breast cancers. The ets proteins share a conserved region of approximately 85 amino acids ETS domain that serves as a DNA-binding domain and recognizes a purine-rich sequence with the core sequence 5-GGAAT-3. In this project, x-ray crystallography and nuclear magnetic resonance NMR are used to determine the structure of the ETS domain of PU.1 alone and complexed to DNA. Atomic models will be used to examine sites in the protein that mediate specific DNA recognition. The structure of the domain will be compared to other DNA-binding motifs to understand the molecular basis for the function of ets-related transcription factors and to evaluate the role of these regulatory elements in the development of leukemia, breast cancer, and other cancers.
- Medicine and Medical Research
- Anatomy and Physiology