title: Alpha-synuclein negatively regulates Notch1 intracellular domain protein stability through promoting interaction with Fbw7.
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.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Hyeong-Jin
authors.initials: HJ
authors.lastname: Baek
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Ann
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Ji-Seon
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Seol-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Jo
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea. Electronic address: proteome@jnu.ac.kr.
authors.forename: Hee-Sae
authors.initials: HS
authors.lastname: Park
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D044783:F-Box Proteins / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D057809:HEK293 Cells; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497761:NOTCH1 protein, human; C497570:RBPJ protein, human; D051881:Receptor, Notch1; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: Alpha-synuclein; Fbw7; Lysosome; Notch1-IC; Proteasome; Ubiquitination