The BAG-1 ULD is required for the interaction of BAG-1 with the proteasome (Luders et al, 2000a), and substantial evidence shows that BAG-1 can act to coordinate the function of chaperones and the proteasome in the degradation of specific proteins (Arndt et al, 2007).
Mutations within helix 2 and 3, but not helix 1, decreased the interaction between BAG-1S and p73 α and reduced the ability of BAG-1S to decrease the expression of p73 α.
The ability of BAG-1 to modulate p73 activity and expression, and to interact with p73 were dependent on amino acid residues required for the interaction of BAG-1 with HSC70 and HSP70.
In addition to the expected association with HSC70, there was a clear interaction between BAG-1S and p73 α.
Previous studies have highlighted the importance of the interaction of Bag-1 and Hsp70 in apoptosis resistance (Townsend et al, 2003b, 2004).
Drugs that bind to the ATP binding site of Hsc70/Hsp70 might also be expected to be effective as they would inhibit the interaction of BAG-1 with the ATPase domain of heat shock proteins.
As shown earlier (Briknarova et al, 2001; Townsend et al, 2004; Lee et al, 2007), mutation of helix 2 and 3, but not helix 1, prevented interaction of BAG-1S with HSC70 in co-immunoprecipitation assays.
In the current paper, we show that Rb function is also required for the anti-apoptotic function of BAG-1 and propose that in addition to regulating E2F-1 activity, Rb may also influence colorectal tumour cell fate through interaction with BAG-1.
Hsp70/Hsc70 interactions with Bag-1 may also be required for an anti-apoptotic function in the cytoplasm.
Wargo, M. J. & Hogan, D. A. Fungal-bacterial interactions: a mixed bag of mingling microbes.
