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学科主题: 临床医学
题名:
Deficiency of hepatocystin induces autophagy through an mTOR-dependent pathway
作者: Yang, Jing2,4; Zhao, Ying2; Ma, Ke2; Jiang, Fen-Jun1; Liao, Wenjuan2; Zhang, Ping2; Zhou, Jingyi2; Tu, Bo2; Wang, Lina2; Kampinga, Harm H.4; Xie, Zhiping1; Zhu, Wei-Guo2,3
关键词: autophagy ; hepatocystin (PRKCSH) ; glucosidase II ; mTOR ; polycystic liver
刊名: AUTOPHAGY
发表日期: 2011-07-01
DOI: 10.4161/auto.7.7.15822
卷: 7, 期:7, 页:748-759
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: POLYCYSTIC LIVER-DISEASE ; ENDOPLASMIC-RETICULUM STRESS ; UNFOLDED PROTEIN RESPONSE ; GLUCOSIDASE-II ; KIDNEY-DISEASE ; BETA-SUBUNIT ; CELL-SIZE ; CALCIUM ; COMPLEX ; YEAST
英文摘要:

Mutations in the gene encoding hepatocystin/80K-H (PRKCSH) cause autosomal-dominant polycystic liver disease (ADPLD). Hepatocystin functions in the processing of nascent glycoproteins as the noncatalytic beta subunit of glucosidase II (Glu II) and regulates calcium release from endoplasmic reticulum (ER) through the inositol-1,4,5-trisphosphate receptor (IP3R). Little is known, however, on how cells respond to a deficiency of hepatocystin. In this study, we demonstrate that knockdown of hepatocystin induces autophagy, the major intracellular degradation pathway essential for cellular health. Ectopic expression of wild-type hepatocystin, but not pathogenic mutants, rescues the siRNA-induced effect. Our data indicate that the induction of autophagy by hepatocystin deficiency is mediated through mammalian target of rapamycin (mTOR). Despite the resulting severe reduction in Glu II activity, the unfolded protein response (UPR) pathway is not disturbed. Furthermore, the inhibition of IP3R-mediated transient calcium flux is not required for the induction of autophagy. These results provide new insights into the function of hepatocysin and the regulation of autophagy.

语种: 英语
所属项目编号: 2011CB910100 ; 2011CB504200 ; 90919030 ; 31070691 ; 30921062 ; 30971441
项目资助者: National Key Basic Research Program of China ; National Natural Science Foundation of China
WOS记录号: WOS:000292300600010
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54071
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Nankai Univ, Sch Med, Tianjin 300071, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Key Lab Carcinogenesis & Translat Res Minist Educ, Beijing 100871, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Sch Oncol, Beijing 100871, Peoples R China
4.Univ Groningen, Dept Cell Biol, Univ Med Ctr Groningen, Groningen, Netherlands

Recommended Citation:
Yang, Jing,Zhao, Ying,Ma, Ke,et al. Deficiency of hepatocystin induces autophagy through an mTOR-dependent pathway[J]. AUTOPHAGY,2011,7(7):748-759.
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