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.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Kim MY,Jung J,Mo JS,Ann EJ,Ahn JS,Yoon JH,Park HSdoi
10.1016/j.yexcr.2011.07.014subject
Has Abstractpub_date
2011-10-15 00:00:00pages
2438-46issue
17eissn
0014-4827issn
1090-2422pii
S0014-4827(11)00300-4journal_volume
317pub_type
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