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Human deltex is a conserved regulator of Notch signalling

Nature Genetics volume 19, pages 74–78 (1998)Cite this article

Abstract

A fundamental cell-fate control mechanism regulating multicellular development is defined by the Notch-signalling pathway1. Developmental and genetic studies of wild type and activated Notch-receptor expression in diverse organisms suggest that Notch plays a general role in development by governing the ability of undifferentiated precursor cells to respond to specific signals1,2. Notch signalling has been conserved throughout evolution and controls the differentiation of a broad spectrum of cell types during development1–3. Genetic studies in Drosophila have led to the identification of several components of the Notch pathway1. Two of the positive regulators of the pathway are encoded by the suppressor of hairless [Su(H)] and deltex (dx) genes5–8. Drosophila dx encodes a ubiquitous, novel cyto-plasmic protein of unknown biochemical function9. We have cloned a human deltex homologue and characterized it in parallel with its Drosophila counterpart in biochemical assays to assess deltex function. Both human and Drosophila deltex bind to Notch across species and carry putative SH3-binding domains. Using the yeast interaction trap system, we find that Drosophila and human deltex bind to the human SH3-domain containing protein Grb2 (ref. 10). Results from two different reporter assays allow us for the first time to associate deltex with Notch-dependent transcriptional events. We present evidence linking deltex to the modulation of basic helix-loop-helix (bHLH) transcription factor activity.

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Author notes

  1. Kenji Matsuno

    Present address: Department of Neuro anatomy, Osaka University Medical School, Osaka, Japan

Authors and Affiliations

  1. Howard Hughes Medical Institute, Department of Cell Biology and Biology Yale University, New Haven, Connecticut, 06536, USA

    Kenji Matsuno, Deborah Eastman, Tim Mitsiades, Anne Marie Quinn & Spyros Artavanis-Tsakonas

  2. Department of Pathology, Yale University, New Haven, Connecticut, 06511, USA

    Maria Louisa Carcanciu

  3. Howard Hughes Medical Institute, Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA

    Peter Ordentlich & Tom Kadesch

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  1. Kenji Matsuno
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Correspondence to Spyros Artavanis-Tsakonas.

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Matsuno, K., Eastman, D., Mitsiades, T. et al. Human deltex is a conserved regulator of Notch signalling. Nat Genet 19, 74–78 (1998). https://doi.org/10.1038/ng0598-74

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