BAG Family Proteins: Regulators of Cancer Cell Growth Through Molecular Chaperones
Abstract
BAG-family proteins regulate diverse cellular functions, including cell survival, cell proliferation, and cell motility. BAG- family proteins contain a conserved domain that allows them to bind 7O-kD heat shock (Hsp70) family molecular chaperones and regulate their activity. Structural analysis of the Hsc70-binding BAG domain of BAG family protein has revealed an anti-parallel two helix bundle, proceeded by an additional long (alpha-helix. Site-directed mutagenesis has confirmed that the polar surfaces of the alpha-helices in the BAG domain are directly involved in chaperone binding, which has been confirmed by NMR experiments (BAGl and BAG4). Similarly, an 80 amino acid region (229-308) of Hsc70 has been determined to represent a minimal domain sufficient for binding the BAG domain. In addition to the Hsp7O-binding domain, BAG-family proteins also contain a diversity of additional domains, which allow them to interact with specific target proteins or which target them to specific locations within cells. The BAG-family proteins operate as bridging molecules that recruit molecular chaperones to target proteins and ultimately affecting diverse cellular behaviors including cell division, migration, differentiation, and death in cancer cells. Recently we found BAG3 as a regulator of cell growth and motility.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407556
Entities
People
- Shinichi Takayama
Organizations
- Sanford Burnham Prebys Medical Discovery Institute