Alpha-synuclein negatively regulates Notch1 intracellular domain protein stability through promoting interaction with Fbw7. (23rd July 2015)

• Record Type: Journal Article
• Authors: Baek, Hyeong-Jin; Yoon, Ji-Hye; Ann, Eun-Jung; Kim, Mi-Yeon; Ahn, Ji-Seon; Kim, Seol-Hee; Jo, Eun-Hye; Lee, Hye-Jin; Park, Hee-Sae
• Is Part Of: Neuroscience letters. Volume 600(2015)
• Page Start: 6
• Page End: 11
• Publication Date: 2015-07-23
• Subjects: Notch1-IC -- Alpha-synuclein -- Fbw7 -- Ubiquitination -- Proteasome -- Lysosome; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2015.05.053
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: 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. 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.