Abstract
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.
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Abbreviations
- RBP-Jk:
-
recombining binding protein suppressor of hairless
- JIP1:
-
JNK-interacting protein-1
- JNK:
-
c-Jun N-terminal kinase
- SH3 domain:
-
Src homology 3 domain
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Acknowledgements
We thank Roger J Davis (University of Massachusetts Medical School, Worcester), JR Woodgett (Ontario Cancer Institute, Toronto), Raphael Kopan (Washington University, St Louis), Alan Israël (Institut Pasteur, Paris), Tasuku Honjo (Kyoto University, Kyoto) for providing JNK1, SAPKb, Notch1, and RBP-Jk cDNA clones. This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A08-4065).
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Kim, MY., Ann, EJ., Mo, JS. et al. JIP1 binding to RBP-Jk mediates cross-talk between the Notch1 and JIP1-JNK signaling pathway. Cell Death Differ 17, 1728–1738 (2010). https://doi.org/10.1038/cdd.2010.50
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DOI: https://doi.org/10.1038/cdd.2010.50
