Direct transactivation of the anti-apoptotic gene apolipoprotein J (clusterin) by B-MYB.
J Biol Chem
; 275(28): 21055-60, 2000 Jul 14.
Article
in En
| MEDLINE
| ID: mdl-10770937
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
Glycoproteins
/
Transcriptional Activation
/
Trans-Activators
/
Promoter Regions, Genetic
/
Molecular Chaperones
/
Cell Cycle Proteins
/
DNA-Binding Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
J Biol Chem
Year:
2000
Document type:
Article
Affiliation country:
Italy