ETS TRANSCRIPTION FACTOR--THE PU.1-DNA COMPLEX

ETS转录因子--PU.1-DNA复合物

• 批准号: 2109552
• 负责人: XIAOPING DAI
• 金额: $ 2.26万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-01-04 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2109552
• 关键词: ETS; TRANSCRIPTION; FACTOR; PU.1; DNA

Transcription factors bind to a specific DNA sequence and regulate important metabolic functions such as cell growth, development and differentiation. There is great interest in understanding the function of these regulatory proteins, especially when their role is linked to oncogenesis. The PU.1 transcription factor is a member of the ets gene family that have been implicated in the development of erythroid leukemia and tumorigenesis in breast cancers. The ets proteins share a conserved region of 85 amino acids (the ETS domain) that binds DNA and recognizes a purine-rich sequence with the core sequence: 5'-GGAA/T-3'. This domain represents a new, yet uncharacterized DNA-binding motif, with no homology to other DNA-binding structures. The PU.1 domain has been crystallized in complex with DNA and high resolution x-ray diffraction data have been collected. In this project, iodinated DNA and heavy metal-substituted protein will be used to solve the crystallographic phases of the complex by multiple isomorphous replacement methods. Atomic models will be used to understand the molecular basis for the function of ets-related transcription factors and to evaluate their role in the development of cancer. The experience gained from the DNA-binding domain will be used to express and purify full-length PU.1 protein for crystallization and structure analysis. This structure will reveal the structure-function relationship of the activation domain to the DNA-binding domain.

转录因子结合到特定的DNA序列并进行调控