A-Myb up-regulates bcl-2 through a Cdx binding site in t(14;18) lymphoma cells

Caroline A. Heckman, John W. Mehew, Guo Guang Ying, Martino Introna, Josee Golay, Linda M. Boxer

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    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)6499-6508
    Number of pages10
    JournalJournal of Biological Chemistry
    Volume275
    Issue number9
    DOIs
    StatePublished - Mar 3 2000

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    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Cite this

    Heckman, C. A., Mehew, J. W., Ying, G. G., Introna, M., Golay, J., & Boxer, L. M. (2000). A-Myb up-regulates bcl-2 through a Cdx binding site in t(14;18) lymphoma cells. Journal of Biological Chemistry, 275(9), 6499-6508. https://doi.org/10.1074/jbc.275.9.6499