Parkin mediates neuroprotection through activation of Notch1 signaling.
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, which promotes neuronal cell survival.
aSchool of Biological Sciences and Technology, Hormone Research Center bDepartment of Chemistry and Institute of Basic Sciences, Chonnam National University, Gwangju, Republic of Korea.
Ji-Hye
JH
Yoon
Eun-Jung
EJ
Ann
Mi-Yeon
MY
Kim
Ji-Seon
JS
Ahn
Eun-Hye
EH
Jo
Hye-Jin
HJ
Lee
Hye-Won
HW
Lee
Young Chul
YC
Lee
Jeong-Sun
JS
Kim
Hee-Sae
HS
Park