Journal
EXPERIMENTAL CELL RESEARCH
Volume 317, Issue 17, Pages 2438-2446Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2011.07.014
Keywords
Notch1-IC; Jagged-1 intracellular domain; Fbw7; RBP-Jk; Mastermind
Categories
Funding
- Ministry of Health and Welfare, Republic of Korea [A090106]
- Korea Health Promotion Institute [A090106] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 Notch] 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. C) 2011 Elsevier Inc. All rights reserved.
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