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- W68298332 abstract "Bcl-2 associated AthanoGene-1 (BAG-1) is a multifunctional protein competent to delay cell death by a synergistic action with Bcl-2. BAG-1, as well as Bcl-2, has been reported as deregulated in diverse cancer types. During PhD study, we confirmed BAG-1 protein as over-expressed in a cohort of leukemic cell lines and heterogeneously expressed in patients affected by de novo acute myeloid or lymphoid leukemia. Silencing approach, used for a determination of BAG-1’s role in AML, suggested a correlation between BAG-1 down-regulation and decreased expression of certain proteins, which contribution to a proliferative advantage of leukemic cells has already been documented.BAG-1 expression in leukemic cells was demonstrated to be reciprocally regulated with the expression of BAG-3, gene from the same family which shows functional similarities with BAG-1. In correspondence, major impact on leukemic cell faith was verified by co-silencing both of this genes. The increased cell death, confirmed after co-silencing of leukemic cell lines and primary AML, was sustained by caspase-3 and PARP cleavage and release of cytochrome c and Smac/DIABLO. Key effect of BAG-1 and BAG-3 co-silencing was seen at the levels of anti-apoptotic proteins Bcl-2, Mcl-1 and Bcl-XL, survival protein ERK1/2 and cyclin D1, which all resulted as decreased. Our results indicated that BAG-1 might take an important place in a protection of native Bcl-2 and Mcl-1 proteins from a proteasome derived degradation, since proteins became removed from cell more intensively after transient BAG-1;3 silencing. In consequence, BAG-1, sustained by BAG-3, occurred to be a novel protein able to affect leukemic cells faith when highly expressed, in major part by provoking in these cells a block of apoptosis induction. It is most likely that described role BAG-1 accomplishes either directly or indirectly. In fact, BAG-1 interacts directly with Bcl-2 and most likely with Usp9X, influencing thereby indirectly the expression of Mcl-1, protein of great importance for leukemic blasts survival, and in consequence impairing the apoptosis induction.Finally, BAG-1 and BAG-3 seem to be new molecules capable to sustain AML. Therefore, identification of their molecular targets, such as Bcl-2, Mcl-1 and Usp9X, significant for leukemia development, gives a meaning to the novel pathways which could be of importance for paediatric AML development and opens a possibility for the future studies for a new therapeutic targets." @default.
- W68298332 created "2016-06-24" @default.
- W68298332 creator A5007677403 @default.
- W68298332 date "2011-01-26" @default.
- W68298332 modified "2023-09-27" @default.
- W68298332 title "Role of BCL-2 associated athanogene - 1 (BAG-1) in Acute Myeloid Leukemia (AML): protein with hundred faces" @default.
- W68298332 hasPublicationYear "2011" @default.
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