BAG3 protein regulates stress- induced apoptosis in normal and neoplastic leukocytes

Co-chaperone proteins that share the Bcl-2-associated athanogene (BAG) domain are characterized by their interaction with a variety of partners, such as heat shock proteins (Hsp), steroid hormone receptors, Bcl-2, Raf-1 and others, involved in regulating protein folding and a number of cellular processes, including proliferation and apoptosis. Among BAG family members there is BAG3, also known as CAIR-1 or Bis. BAG3 forms a complex with Hsp70,1,2,4,6 a protein able to modulate apoptosis by interfering with cytochrome c release, apoptosome assembly and other events in the death process. In addition, BAG3 polypeptide binds to phospholipase C-g (PLC-g)4 or Bcl-2 protein.3,5 Due to such interaction with more than one apoptosis-modulating factor, BAG3 can participate in apoptosis regulation. Indeed, its hyperexpression can decrease apoptosis induced via Bax or Fas in the human epithelial cell line HeLa3 or by IL-3 deprivation in the murine hematopoietic cell line 32D.5 Furthermore, we recently showed that BAG3 downmodulation enhances the apoptotic response to chemotherapy in human primary B chronic lymphocytic leukemia cells