Apoptosis inhibition in cancer cells: a novel molecular pathway that involves BAG3 protein.
Stress-induced apoptosis regulates neoplasia pathogenesis and response to therapy. Indeed, cell transformation induces a stress response, that is overcome, in neoplastic cells, by alterations in apoptosis modulators; on the other hand, antineoplastic therapies largely trigger the apoptosis stress pathway, whose impairment results in resistance. Therefore, the study of the roles of apoptosis-modulating molecules in neoplasia development and response to therapy is of key relevance for our understanding of these processes. Among molecules that regulate apoptosis, a role is emerging for BAG3, a member of the BAG co-chaperone protein family. Proteins that share the BAG domain are characterized by their interaction with a variety of partners (heat shock proteins, steroid hormone receptors, Raf-1 and others), involved in regulating a number of cellular processes, including proliferation and apoptosis. BAG3, also known as CAIR-1 or Bis, forms a complex with the heat shock protein (Hsp) 70. This assists polypeptide folding, can mediate protein delivery to proteasome and is able to modulate apoptosis by interfering with cytochrome c release, apoptosome assembly and other events in the death process. It has been recently shown that, in human primary lymphoid and myeloblastic leukemias and other neoplastic cell types, BAG3 expression sustains cell survival and underlies resistance to therapy, through downmodulation of apoptosis. This review summarizes findings that assign an apoptotic role to BAG3 in some neoplastic cell types and identify the protein as a candidate target of therapy.
Rosati
Alessandra
A
Department of Pharmaceutical Sciences, University of Salerno, via ponte don Melillo, 84084 Fisciano, Italy.
Ammirante
Massimo
M
Gentilella
Antonio
A
Basile
Anna
A
Festa
Michela
M
Pascale
Maria
M
Marzullo
Liberato
L
Belisario
Maria Antonietta
MA
Tosco
Alessandra
A
Franceschelli
Silvia
S
Moltedo
Ornella
O
Pagliuca
Gabriella
G
Lerose
Rosa
R
Turco
Maria Caterina
MC
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D018840:HSP70 Heat-Shock Proteins