Involvement of a proline-rich motif and RING-H2 finger of Deltex in the regulation of Notch signaling

Kenji Matsuno, Mikiko Ito, Kazuya Hori, Fumiyasu Miyashita, Satoshi Suzuki, Noriyuki Kishi, Spyros Artavanis-Tsakonas, Hideyuki Okano

Research output: Contribution to journalReview article

84 Citations (Scopus)

Abstract

The Notch pathway is an evolutionarily conserved signaling mechanism that is essential for cell-cell interactions. The Drosophila deltex gene regulates Notch signaling in a positive manner, and its gene product physically interacts with the intracellular domain of Notch through its N-terminal domain. Deltex has two other domains that are presumably involved in protein-protein interactions: a proline-rich motif that binds to SH3-domains, and a RING-H2 finger motif. Using an overexpression assay, we have analyzed the functional involvement of these Deltex domains in Notch signaling. The N-terminal domain of Deltex that binds to the CDC10/Ankyrin repeats of the Notch intracellular domain was indispensable for the function of Deltex. A mutant form of Deltex that lacked the proline-rich motif behaved as a dominant-negative form. This dominant-negative Deltex inhibited Notch signaling upstream of an activated, nuclear form of Notch and downstream of full-length Notch, suggesting the dominant-negative Deltex might prevent the activation of the Notch receptor. We found that Deltex formed a homo-multimer, and mutations in the RING-H2 finger domain abolished this oligomerization. The same mutations in the RING-H2 finger motif of Deltex disrupted the function of Deltex in vivo. However, when the same mutant was fused to a heterologous dimerization domain (Glutathione-S-Transferase), the chimeric protein had normal Deltex activity. Therefore, oligomerization mediated by the RING-H2 finger motif is an integral step in the signaling function of Deltex.

Original languageEnglish
Pages (from-to)1049-1059
Number of pages11
JournalDevelopment
Volume129
Issue number4
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • Cell-cell interaction
  • Deltex
  • Drosophila
  • Notch
  • RING-H2 finger
  • SH3-domain
  • Wing formation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Matsuno, K., Ito, M., Hori, K., Miyashita, F., Suzuki, S., Kishi, N., Artavanis-Tsakonas, S., & Okano, H. (2002). Involvement of a proline-rich motif and RING-H2 finger of Deltex in the regulation of Notch signaling. Development, 129(4), 1049-1059.