BACE1 SUMOylation deregulates phosphorylation and ubiquitination in Alzheimer's disease pathology

被引：8

作者：

Zhao, Yanna ^{[1
,2
]}

Zhou, Hongyan ^{[1
,2
]}

Zhao, Yan ^{[1
]}

Liang, Zhen ^{[1
]}

Gong, Xiaokang ^{[1
]}

Yu, Jing ^{[1
,2
]}

Huang, Tiantian ^{[1
,2
]}

Yang, Chaoqin ^{[1
,2
]}

Wu, Mengjuan ^{[1
,2
]}

Xiao, Yifan ^{[1
,2
]}

Yang, Youhua ^{[1
,3
]}

Liu, Wei ^{[1
,2
]}

Wang, Xiaochuan ^{[1
,4
]}

Shu, Xiji ^{[1
,2
,5
]}

Bao, Jian ^{[1
,2
,5
]}

机构：

[1] Jianghan Univ, Inst Biomed Sci, Sch Med, Wuhan, Peoples R China

[2] Jianghan Univ, Sch Med, Dept Pathol & Pathophysiol, Wuhan, Peoples R China

[3] Jianghan Univ, Sch Med, Dept Physiol, Wuhan, Peoples R China

[4] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathophysiol,Key Lab Educ Minist China Ne, Wuhan, Peoples R China

[5] Jianghan Univ, Inst Biomed Sci, Sch Med, Wuhan 430056, Peoples R China

来源：

JOURNAL OF NEUROCHEMISTRY | 2023年 / 166卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Alzheimer's disease; amyloid-beta; BACE1; phosphorylation; SUMOylation; ubiquitination; BETA-SECRETASE; TRAFFICKING; SUMO; DEGRADATION; MOTIF;

D O I：

10.1111/jnc.15870

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

BACE1 is essential for the generation of amyloid-beta (A alpha) that likely initiates the toxicity in Alzheimer's disease (AD). BACE1 activity is mainly regulated by post-translational modifications, but the relationship between these modifications is not fully characterized. Here, we studied the effects of BACE1 SUMOylation on its phosphorylation and ubiquitination. We demonstrate that SUMOylation of BACE1 inhibits its phosphorylation at S498 and its ubiquitination in vitro. Conversely, BACE1 phosphorylation at S498 suppresses its SUMOylation, which results in promoting BACE1 degradation in vitro. Furthermore, an increase in BACE1 SUMOylation is associated with the progression of AD pathology, while its phosphorylation and ubiquitination are decreased in an AD mouse model. Our findings suggest that BACE1 SUMOylation reciprocally influences its phosphorylation and competes against its ubiquitination, which might provide a new insight into the regulations of BACE1 activity and A beta accumulation.

引用

页码：318 / 327

页数：10

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