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Notchi and EBV

Intracellular forms of human NOTCH1 interact at distinctly different levels with RBP-Jkappa in human B and T cells

Leukemia volume 14, pages 84–92 (2000)Cite this article

Abstract

The cellular transcriptional repressor RBP-Jκ associates with the Epstein–Barr virus nuclear antigens (EBNAs) determined to be essential for transformation of human primary B lymphocytes. It was demonstrated through genetic analysis that interaction between the viral transactivator EBNA2 and RBP-Jκ is essential for EBV immortalization of primary B lymphocytes. We have shown that the association of RBP-Jκ with intracellular NOTCH1 differs significantly in B and T cells. Immunoprecipitation analyses with antibodies to both the intracellular forms of NOTCH1 and to RBP-Jκ demonstrated that little or no RBP-Jκ is associated with NOTCH1 in B cell lines compared to the RBP-Jκ associated with NOTCH1 in T cell lines and was further demonstrated in human primary lymphocytes. Additionally, EBNA2 can compete with intracellular NOTCH1 for binding to GST-RBP-Jκ in vitro. Northern blot for the cellular gene hairy enhancer of split (HES1) demonstrated that HES1 is upregulated in the EBV transformed lymphoblastoid cells expressing high levels of EBNA2 and in a T cell line SupT1 overexpressing intracellular activated NOTCH1. Hence, EBNA2 may be able to compete for the available pool of RBP-Jκ more effectively in human B cells than in T cells and provides a possible explanation for the ability of EBV to potently and efficiently infect and immortalize human B cells.

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Acknowledgements

ESR is a Scholar of the Leukemia Society of America. This work was supported by grants from the Leukemia Society of America, the American Heart Association (to ESR) and National Cancer Institute Grants CA66849 (to JCA), CA47006 (to EDK), CA62450 (to JS) and CA072150 (to ESR).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA

    J Callahan & ES Robertson

  2. Division of Molecular Oncology, Department of Pathology, Brigham and Women's Hospital Harvard Medical School, Boston, MA, USA

    J Aster & J Sklar

  3. Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital and Program in Virology, Harvard Medical School, Boston, MA, USA

    E Kieff

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Callahan, J., Aster, J., Sklar, J. et al. Intracellular forms of human NOTCH1 interact at distinctly different levels with RBP-Jkappa in human B and T cells. Leukemia 14, 84–92 (2000). https://doi.org/10.1038/sj.leu.2401630

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