title: 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.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.forename: Jane
authors.initials: J
authors.lastname: Jung
authors.forename: Jung-Soon
authors.initials: JS
authors.lastname: Mo
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Ann
authors.forename: Ji-Seon
authors.initials: JS
authors.lastname: Ahn
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Yoon
authors.forename: Hee-Sae
authors.initials: HS
authors.lastname: Park
mesh_terms: D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D044783:F-Box Proteins / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051881:Receptor, Notch1 / Q000737:chemistry* / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D044767:Ubiquitin-Protein Ligases