Cervellera, M;
Raschella, G;
Santilli, G;
Tanno, B;
Ventura, A;
Mancini, C;
Sevignani, C;
... Sala, A; + view all
(2000)
Direct Transactivation of the Anti-apoptotic Gene Apolipoprotein J (Clusterin) by B-MYB.
Journal of Biological Chemistry
, 275
(28)
pp. 21055-21060.
10.1074/jbc.M002055200.
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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 progression. 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/Clusterin 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
| Type: | Article |
|---|---|
| Title: | Direct Transactivation of the Anti-apoptotic Gene Apolipoprotein J (Clusterin) by B-MYB |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1074/jbc.M002055200 |
| Publisher version: | https://doi.org/10.1074/jbc.M002055200 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | BC, GENE, Animals Base Sequence COS Cells *Cell Cycle Proteins Clusterin DNA-Binding Proteins/*metabolism Glycoproteins/biosynthesis/*genetics Humans *Molecular Chaperones Molecular Sequence Data Neoplasm Proteins/genetics Neuroblastoma Oncogene Proteins/metabolism |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10110439 |
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