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Alpha-synuclein negatively regulates Notch1 intracellular domain protein stability through promoting interaction with Fbw7.
- Source :
-
Neuroscience Letters . Jul2015, Vol. 600, p6-11. 6p. - Publication Year :
- 2015
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03043940
- Volume :
- 600
- Database :
- Academic Search Index
- Journal :
- Neuroscience Letters
- Publication Type :
- Academic Journal
- Accession number :
- 108341232
- Full Text :
- https://doi.org/10.1016/j.neulet.2015.05.053