The intracellular domain of Jagged-1 interacts with Notch1 intracellular domain and promotes its degradation through Fbw7 E3 ligase |
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Authors: | Kim Mi-Yeon Jung Jane Mo Jung-Soon Ann Eun-Jung Ahn Ji-Seon Yoon Ji-Hye Park Hee-Sae |
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Institution: | aHormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea |
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Abstract: | Notch signaling involves the proteolytic cleavage of the transmembrane Notch receptor after binding to its transmembrane ligands. Jagged-1 also undergoes proteolytic cleavage by gamma-secretase and releases an intracellular fragment. In this study, we have demonstrated that the Jagged-1 intracellular domain (JICD) inhibits Notch1 signaling via a reduction in the protein stability of the Notch1 intracellular domain (Notch1-IC). The formation of the Notch1-IC-RBP-Jk-Mastermind complex is prevented in the presence of JICD, via a physical interaction. Furthermore, JICD accelerates the protein degradation of Notch1-IC via Fbw7-dependent proteasomal pathway. These results indicate that JICD functions as a negative regulator in Notch1 signaling via the promotion of Notch1-IC degradation. |
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Keywords: | Notch1-IC Jagged-1 intracellular domain Fbw7 RBP-Jk Mastermind |
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