کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4343376 | 1615099 | 2015 | 6 صفحه PDF | دانلود رایگان |
• SNCA attenuates Notch1-IC-mediated transcriptional activity.
• SNCA inhibits interaction between Notch1-IC and RBP-Jκ.
• SNCA promotes interaction between Notch1-IC and Fbw7.
• SNCA increases Fbw7-mediated degradation of Notch1-IC.
Notch signaling pathway is well known that it is involved in regulating cell fate, proliferation and homeostasis. In this study, we show a novel function of alpha-synuclein (SNCA) to promote degradation of Notch1 intracellular domain (Notch1-IC) through Fbw7, ubiquitin E3 ligase. We identified that SNCA inhibits Notch1 transcription activity and diminishes the interaction between Notch1-IC and RBP-Jk. We also found decrease of Notch1-IC protein stability by exogenous and endogenous SNCA through proteasomal pathway, not through lysosomal pathway. And, we found that SNCA promotes interaction between Notch1-IC and Fbw7. Furthermore, SNCA directly interacts with Fbw7. SNCA increases ubiquitination of Notch-IC by Fbw7 through interaction with Fbw7. Together, these results suggest that SNCA is a novel regulator of Notch1-IC transcriptional activity with acting as an enhancer of the interaction of Notch1-IC and Fbw7 with increasing degradation of Notch1-IC.
Journal: Neuroscience Letters - Volume 600, 23 July 2015, Pages 6–11