Structure and Function of the AIB1 (Amplified in Breast Cancer-1) Protein
Abstract
The overexpression or amplification of the AIB1 gene is observed in the majority of primary breast tumors, and is also correlated with a large percentage of hereditary and sporadic ovarian carcinomas. The AIB1 protein is a member of the steroid receptor coactivator family of transcriptional regulatory proteins that contain a conserved C-terminal histone acetyltransferase domain, and an N-terminal bHLH-PAS domain. The authors hypothesize that the HAT and bHLH-PAS domains of AIB1 play critical roles in mediating elevated transcriptional activation levels in AIB1-mediated cancers. The goal of this proposal is to determine the three-dimensional structure of the HAT and bHLH-PAS domains of AIB1 to facilitate the structure-based design of small molecule inhibitors to specifically target AIB1 for therapeutic application. To date, the authors have prepared several HAT and bHLH-PAS-containing AIB1 recombinants. Each of the HAT-containing domains, either alone or as GST fusion proteins, are unstable, suggesting that the HAT domain is not correctly folded and may require association with another protein factor for AIB1-mediated HAT activity. They have overexpressed and purified to homogeneity several N-terminal bHLH-PAS-containing domains that migrate as apparent monomers on gel filtration chromatography. Crystallization efforts to these bHLH-PAS-containing AIB1 domains are underway to facilitate an X-ray crystal structure determination. (15 refs.)
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418064
Entities
People
- Ronen Marmorstein
Organizations
- University of Pennsylvania