Document Detail

Direct transactivation of the anti-apoptotic gene apolipoprotein J (clusterin) by B-MYB.
MedLine Citation:
PMID:  10770937     Owner:  NLM     Status:  MEDLINE    
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.
M Cervellera; G Raschella; G Santilli; B Tanno; A Ventura; C Mancini; C Sevignani; B Calabretta; A Sala
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-08-16     Completed Date:  2000-08-16     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  21055-60     Citation Subset:  IM    
Laboratory of Molecular Pharmacology and Pathology, Consorzio Mario Negri Sud, 66030 S. Maria Imbaro, Italy.
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MeSH Terms
Base Sequence
COS Cells
Cell Cycle Proteins*
DNA-Binding Proteins / metabolism*
Glycoproteins / biosynthesis,  genetics*
Molecular Chaperones*
Molecular Sequence Data
Neoplasm Proteins / genetics
Oncogene Proteins / metabolism
Promoter Regions, Genetic*
RNA, Messenger / genetics
Recombinant Proteins / biosynthesis
Sequence Alignment
Sequence Homology, Nucleic Acid
Trans-Activators / metabolism*
Transcription, Genetic*
Transcriptional Activation*
Tumor Cells, Cultured
Reg. No./Substance:
0/CLU protein, human; 0/Cell Cycle Proteins; 0/Clusterin; 0/DNA-Binding Proteins; 0/Glycoproteins; 0/MYBL2 protein, human; 0/Molecular Chaperones; 0/Neoplasm Proteins; 0/Oncogene Proteins; 0/RNA, Messenger; 0/Recombinant Proteins; 0/Trans-Activators

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