Autophagy, 2015, 01, 100─112

SUMO1 promotes Aβ production via the modulation of autophagy

Sun-Jung Cho, Sang-Moon Yun, Chulman Jo, Dae-hoon Lee, Ki Ju Choi, Jae Chun Song, Sang Ick Park, You-Jin Kim, Young Ho Koh

Abstract

Autophagy is one of the main mechanisms in the pathophysiology of neurodegenerative disease. The accumulation of autophagic vacuoles (AVs) in affected neurons is responsible for amyloid-b (Ab) production. Previously, we reported that SUMO1 (small ubiquitin-like modifier 1) increases Ab levels. In this study, we explored the mechanisms underlying this. We investigated whether AV formation is necessary for Ab production by SUMO1. Overexpression of SUMO1 increased autophagic activation, inducing the formation of LC3-II-positive AVs in neuroglioma H4 cells. Consistently, autophagic activation was decreased by the depletion of SUMO1 with small hairpin RNA (shRNA) in H4 cells. The SUMO1-mediated increase in Ab was reduced by the autophagy inhibitors (3-methyladenine or wortmannin) or genetic inhibitors (siRNA targeting ATG5, ATG7, ATG12, or HIF1A/, respectively. Accumulation of SUMO1, ATG12, and LC3 was seen in amyloid precursor protein transgenic mice. Our results suggest that SUMO1 accelerates the accumulation of AVs and promotes Ab production, which is a key mechanism for understanding the AV-mediated pathophysiology of Alzheimer disease.

• ISBN or ISSN: 1554-8627

• 본 연구는 질병관리본부 연구개발과제(과제번호 2013-NC62001-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2013-NC62001-00) by Research of Korea Centers for Disease Control and Prevention.