BAG3: a multifaceted protein that regulates major cell pathways

Rosati, A; Graziano, V; De Laurenzi, V; Pascale, M; Turco, M C

From the first evidence of BAG3-mediated survival in B-CLLs, 21 a number of reports confirmed the anti-apoptotic activity of the protein in tumors of the hematopoietic 2, 13, 21, 22, 25, 28, 30, 39, 40, 49 and other 2, 20, 24, 25, 29, 31, 34, 36, 37, 44 compartments. Two principal elements contribute to the role of BAG3 in vast range of tumors: bag3 induction by HSF1, 47 a transcription factor activated in many cancer types; 46 and BAG3 ability to sustain of NF-kB activity. 76 In addition, BAG3, because of its multifaceted ability to complex with many proteins, can regulate factors that are particularly relevant in the context of specific tumor types, such as BAX in glioblastoma cells. 36 Overall, studies on BAG3 expression and activity in normal and neoplastic cells, and of its regulation during the development, increasingly delineate a complex picture of BAG3 involvement in physiological and pathological processes. The pleiotropic functions attributed to BAG3 probably reflect the adapter nature of this multidomain (BAG, WW and PXXP) protein and its ability to assemble scaffolding complexes, which participate in more than one signal transduction pathway.