Jun 3, 2015

Alpha-synuclein negatively regulates Notch1 intracellular domain protein stability through promoting interaction with Fbw7

Neuroscience Letters
Hyeong-Jin BaekHee-Sae Park

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.

  • References17
  • Citations2

Mentioned in this Paper

Study
Biochemical Pathway
SNCA gene
Cell Fate
HEK293 Cells
Cell Cycle Proteins
Notch
F-Box Proteins
Regulation of Biological Process
Ubiquitin

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