Page 148 - ebook
P. 148
[B. Cell Biology/Stem Cell] B-9
Parkin facilitates neuronal protection through activation of
Notch1
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
Parkin, an E3 ubiquitin ligase, is the most frequently mutated gene in hereditary Parkinson’s disease. Inactivation of
Parkin leads to impairment of the ubiquitin–proteasome system, resulting in the accumulation of misfolded or
aggregated proteins and ensuing neurodegeneration. In this study, we show that Parkin positively regulates the
Notch1 signaling pathway. Overexpression of Parkin stabilized Notch1-IC protein levels, whereas knockdown of
Parkin decreased Notch1-IC protein stability. Notably, overexpression of Parkin disrupted oxidative stress-induced
apoptosis in neuronal cells. However, knockdown of Notch1 inhibited Parkin-induced neuronal cell survival. Together,
these results indicate that Parkin is a novel regulator of the Notch1 signaling pathway,
