Page 152 - ebook

[B. Cell Biology/Stem Cell] B-11

Alpha-synuclein regulates ubiquitination of Notch1-IC by

Fbw7

Eun-Hye Jo¹, Mi-Yeon Kim¹, So-I Noh¹, Hyung-Ju Lee¹, Hee-Sae Park¹*

¹School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Korea

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.