Novel Targets for Apoptosis Modulation: BAG3 Protein and Other Co- Chaperones

Deregulation of apoptosis is responsible for diseases that involve defects in the death pathway, such as neoplasias, or in its inhibition, like degenerative processes. Among apoptosis- regulating molecules, a role is emerging for BAG3, a member of the BAG proteins family (BAG1L, BAG1, BAG2, BAG3, BAG4. BAG5 and BAG6) involved in cochaperoning of heat shock proteins. Through its BAG, WW and prolix-rich domains, BAG3 protein can interact with a variety of molecular partners, including Hsc70/Hsp70, phospholipase C-γ and others. It has been recently shown that, in human primary lymphoid and myeloblastic leukemias, thyroid carcinoma and other human tumors, BAG3 expression sustains cell survival and impairs cell response to therapy. This review discusses two patents concerning, respectively, BAG3 and other Hsc70/Hsp70 co-chaperones, namely HspBP-1 and HspBP-2.