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.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Calcium-Binding Proteins / chemistry*
-
Calcium-Binding Proteins / metabolism*
-
Cell Cycle Proteins / metabolism*
-
Cells, Cultured
-
Down-Regulation
-
F-Box Proteins / metabolism*
-
F-Box-WD Repeat-Containing Protein 7
-
HEK293 Cells
-
Humans
-
Intercellular Signaling Peptides and Proteins / chemistry*
-
Intercellular Signaling Peptides and Proteins / metabolism*
-
Jagged-1 Protein
-
Membrane Proteins / chemistry*
-
Membrane Proteins / metabolism*
-
Protein Structure, Tertiary
-
Receptor, Notch1 / chemistry*
-
Receptor, Notch1 / metabolism*
-
Serrate-Jagged Proteins
-
Signal Transduction
-
Ubiquitin-Protein Ligases / metabolism*
Substances
-
Calcium-Binding Proteins
-
Cell Cycle Proteins
-
F-Box Proteins
-
F-Box-WD Repeat-Containing Protein 7
-
FBXW7 protein, human
-
Intercellular Signaling Peptides and Proteins
-
JAG1 protein, human
-
Jagged-1 Protein
-
Membrane Proteins
-
NOTCH1 protein, human
-
Receptor, Notch1
-
Serrate-Jagged Proteins
-
Ubiquitin-Protein Ligases