Structural Characterization of a Novel HER2/neu Binding Ets Factor, ESX
Abstract
Understanding the structural basis of protein-nucleic interactions involved in breast cancer cell proliferation would prove beneficial to the rational design of therapeutic strategies aimed at reducing proliferation. We have focused on two proteins, ESX and Fmu, which serve as models for understanding the structural role of protein- nucleic acid interactions in the growth control of breast cancer. ESX, an Ets family transcription factor, binds to the Ets response element of the HER2 promoter and upregulates HER2 transcription. Fmu, a cytosine methyltransferase that modifies rRNA, is the bacterial homolog of human nucleolar p120, an enzyme overexpressed in human breast tumors and likely critical to the proliferative phenotype. The research goal is to determine these protein structures by x-ray crystallography and define the specific contacts with their binding targets to enable the design of small molecule modulators of proliferative function. As crystals of ESX have not been obtained, we have focused on Fmu structure determination. We present the structures of Fmu alone, and an Fmu-cofactor complex. Structure determination of Fmu will provide insight into RNA binding and modification, and present a novel target for breast cancer intervention
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA398281
Entities
People
- C. Benz
- C. Nunes
Organizations
- University of California, San Francisco