Notch Activation by Shootin1 Opposing Activities on 2 Ubiquitin Ligases
| Autor: | Jane McGlade, Orly Reiner, Irina Shin, Vanessa Zamor, Rebecca Haffner-Krausz, Noga Kozer, Tamar Sapir, Talia Levy |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neurogenesis Ubiquitin-Protein Ligases Cognitive Neuroscience Notch signaling pathway Nerve Tissue Proteins Cell fate determination Mice 03 medical and health sciences Cellular and Molecular Neuroscience Neural Stem Cells Ubiquitin Neuroblast Animals Mice Knockout Receptors Notch biology Chemistry Cell Differentiation Transmembrane protein Cell biology Ubiquitin ligase Enzyme Activation 030104 developmental biology Proteasome biology.protein NUMB Signal Transduction |
| Zdroj: | Cerebral Cortex. 28:3115-3128 |
| ISSN: | 1460-2199 1047-3211 |
| Popis: | The evolutionarily conserved Notch pathway plays an important role in regulation of stem cell renewal and cell fate determination in numerous organs, and as such is a key pathway in normal health and disease processes. Canonical Notch signaling is usually activated by cell contact where transmembrane ligands such as Delta-like and Jagged bind to Notch receptors. Notch activation results in the translocation of the cleaved Notch intracellular domain (NICD) into the nucleus and subsequent activation of transcription. Poly-ubiquitination leading to proteosome degradation of pathway components is one mean of regulating the Notch pathway. Here, we identified that Shootin1 exhibits the surprising propensity of activating the pathway either by interacting with LNX1/2 and promoting poly-ubiquitination of Numb or by complexing with Itch and impairing poly-ubiquitination of NICD. Within the developing brain Shootin1 modulates neuroblasts cell fate by executing 2 opposing activities on ubiquitin ligases, which control Notch signaling on 2 different levels. |
| Databáze: | OpenAIRE |
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