Direct transactivation of the anti-apoptotic gene apolipoprotein J (Clusterin) by B-MYB

Maria Cervellera, Giuseppe Raschella, Giorgia Santilli, Barbara Tanno, Andrea Ventura, Camillo Mancini, Cinzia Sevignani, Bruno Calabretta, Arturo Sala

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Abstract

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.
Original languageEnglish
Pages (from-to)21055 - 21060
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number28
DOIs
Publication statusPublished - 14 Jul 2000
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

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