JIP1 binding to RBP-Jk mediates cross-talk between the Notch1 and JIP1-JNK signaling pathway

M. Y. Kim, E. J. Ann, J. S. Mo, F. Dajas-Bailador, M. S. Seo, J. A. Hong, J. Jung, Y. H. Choi, J. H. Yoon, S. M. Kim, E. J. Choi, H. S. Hoe, A. J. Whitmarsh, H. S. Park

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Notch1 signaling has a critical function in maintaining a balance among cell proliferation, differentiation, and apoptosis. Our earlier work showed that the Notch1 intracellular domain interferes with the scaffolding function of c-Jun N-terminal kinase (JNK)-interacting protein-1 (JIP1), yet the effect of JIP1 for Notch1-recombining binding protein suppressor of hairless (RBP-Jk) signaling remains unknown. Here, we show that JIP1 suppresses Notch1 activity. JIP1 was found to physically associate with either intracellular domain of Notch1 or RBP-Jk and interfere with the interaction between them. Furthermore, we ascertained that JIP1 caused the cytoplasmic retention of RBP-Jk through an interaction between the C-terminal region of JIP1 including Src homology 3 domain and the proline-rich domain of RBP-Jk. We also found that RBP-Jk inhibits JIP1-mediated activation of the JNK1 signaling cascade and cell death. Our results suggest that direct protein-protein interactions coordinate cross-talk between the Notch1-RBP-Jk and JIP1-JNK pathways.

Original languageEnglish
Pages (from-to)1728-1738
Number of pages11
JournalCell Death and Differentiation
Issue number11
Publication statusPublished - 2010 Nov


  • JIP1
  • Notch1
  • RBP-Jk
  • SH3 domain
  • cytoplasmic retention

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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