REGULATION OF THE HEAT-SHOCK COGNATE HSC70 IN THE MAMMALIAN-CELL - THE CHARACTERIZATION OF THE ANTI-APOPTOTIC PROTEIN BAG-1 PROVIDES NOVEL INSIGHTS

The regulation of the chaperone activity of the heat shock cognate Hsc 70 protein in the mammalian cell involves a cooperation with chaperone cofactors such as Hsp40, the Hsp70-interacting protein Hip, and the H sc70/Hsp90-organizing protein Hop. Recent studies have now added anoth er component to the list of Hsc70 cofactors, the BAG-1 protein. Initia lly identified as an anti-apoptotic molecule and binding partner of th e cell death inhibitor Bcl-2, BAG-1 appears to fulfill its cellular fu nction through a modulation of Hsc70's chaperone activity. BAG-1 acts as a nucleotide exchange factor in the Hsc70 ATPase cycle, thereby com peting with the cofactor Hip which stabilizes the ADP-bound state of H sc70. The functional characterization of BAG-1 thus reveals an unexpec ted versatility in the regulation of Hsc70 and appears to provide a li nk between apoptosis and the cellular chaperone machinery.