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 cell