Document Detail

A-Myb up-regulates Bcl-2 through a Cdx binding site in t(14;18) lymphoma cells.
MedLine Citation:
PMID:  10692454     Owner:  NLM     Status:  MEDLINE    
In follicular lymphoma, bcl-2 is translocated to the immunoglobulin heavy chain locus leading to deregulation of bcl-2 expression. We examined the role of Myb proteins in the regulation of bcl-2 expression in lymphoma cells. We showed that A-Myb up-regulates bcl-2 promoter activity. Northern and Western analyses demonstrated that A-Myb was expressed in the DHL-4 t(14;18) cell line. In t(14;18) cells and mature B cells, A-Myb up-regulated bcl-2 expression, whereas B- and c-Myb had little effect on bcl-2 gene expression. Deletion analysis of the bcl-2 5'-region identified a region responsive to A-Myb in t(14;18) cells. A potential binding site for the Cdx homeodomain proteins was located in this sequence. Analysis of the A-Myb-responsive region by UV cross-linking experiments revealed that a 32-kDa protein formed a complex with this region, but direct binding by Myb proteins could not be demonstrated. A-Myb could be recovered along with Cdx2 when nuclear extracts were passed over the Cdx site. Mutagenesis of the Cdx binding site abolished binding by the 32-kDa protein and significantly reduced the ability of A-Myb to induce bcl-2 expression. A strong induction of bcl-2 P2 promoter activity was observed in cotransfection studies of DHL-4 cells with the A-Myb and Cdx2 expression vectors, and increased endogenous Bcl-2 protein expression was observed in B cells transfected with A-Myb and/or Cdx2 expression constructs.
C A Heckman; J W Mehew; G G Ying; M Introna; J Golay; L M Boxer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-04-03     Completed Date:  2000-04-03     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:  6499-508     Citation Subset:  IM    
Center for Molecular Biology in Medicine, Veterans Affairs Palo Alto Health Care System and the Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
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MeSH Terms
Binding Sites
DNA-Binding Proteins / genetics
Gene Expression Regulation, Neoplastic / genetics*
Homeodomain Proteins / genetics*
Lymphoma, Follicular
Promoter Regions, Genetic
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-bcl-2 / metabolism*
RNA, Messenger / metabolism
Trans-Activators / metabolism*
Translocation, Genetic / genetics*
Tumor Cells, Cultured
Ultraviolet Rays
Up-Regulation / genetics
Grant Support
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Homeodomain Proteins; 0/MYBL1 protein, human; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Messenger; 0/Trans-Activators; 156560-97-3/Cdx-2-3 protein

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