The intracellular domain of Jagged-1 interacts with Notch1 intracellular domain and promotes its degradation through Fbw7 E3 ligase.

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 Res

authors

Kim MY,Jung J,Mo JS,Ann EJ,Ahn JS,Yoon JH,Park HS

doi

10.1016/j.yexcr.2011.07.014

subject

Has Abstract

pub_date

2011-10-15 00:00:00

pages

2438-46

issue

17

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(11)00300-4

journal_volume

317

pub_type

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