B-MYB is a ubiquitously expressed transcription factor involved in the regulation of cell survival, proliferation, and differentiation. In an attempt to isolate B-MYB-regulated genes that may explain the role of B-MYB in cellular processes, representational difference analysis was performed in neuroblastoma cell lines with different levels of B-MYB expression. One of the genes, the mRNA levels of which were enhanced in B-MYB expressing cells, was ApoJ/Clusterin(SGP-2/TRMP-2) (ApoJ/Clusterin), previously implicated in regulation of apoptosis and tumor progress/on. Here we show that the human ApoJ/Clusterin gene contains a Myb binding site in its 5' flanking region, which interacts with bacterially synthesized B-MYB protein and mediates B- MYB-dependent transactivation of the ApoJ/Clusterin promoter in transient transfection assays. Endogenous ApoJ/Cluster/n expression is induced in mammalian cell lines following transient transfection of a B-MYB cDNA. Blockage of secreted clusterin by a monoclonal antibody results in increased apoptosis of neuroblastoma cells exposed to the chemotherapeutic drug doxorubicin. Thus, activation of ApoJ/Clusterin by B-MYB may be an important step in the regulation of apoptosis in normal and diseased cells.
All Science Journal Classification (ASJC) codes
Cervellera, M., Raschella, G., Santilli, G., Tanno, B., Ventura, A., Mancini, C., ... Sala, A. (2000). Direct transactivation of the anti-apoptotic gene apolipoprotein J (Clusterin) by B-MYB. Journal of Biological Chemistry, 275(28), 21055 - 21060. https://doi.org/10.1074/jbc.M002055200