BAG Family Proteins: Regulators of Cancer Cell Growth Through Molecular Chaperones
Annual rept. 1 Jun 1999-31 May 2000
BURNHAM INST LA JOLLA CA
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BAG-1 is a novel regulator of Hsp7O family molecular chaperones. The activity of many steroid hormone receptors, including the estrogen receptor, ERalpha, is known to be regulated by Hsp70 and Hsp9O family proteins. A carboxyl terminal domain of BAG-I binds to the ATPase domain of Hsc70Hsp70 and regulates its chaperone function. We have cloned two additional novel BAG-i homologs BAG-2, BAG-3 using yeast two hybrid screening with the Hsc70 ATPase doimain as a bait. In addition we have identified two more possible BAG homologs in the EST database. The fundamental hypothesis we propose to test is that BAG family proteins are important regulators of ER function in breast cancers. In the first year of this research proposal, we cloned fell length cDNA of BAG family proteins. Predicted amino acid sequence shows that all member of these protein has the similar sequence in the c-terminal homologous domain and diverse sequence in N-terminus domain. Several kinds of antibody against BAG family proteins have been generated using GST fusion protein and we have preliminary data about the western analysis of breast cancer cell lines.
- Anatomy and Physiology
- Medicine and Medical Research