Physiological levels of ATP negatively regulate proteasome function

被引：108

作者：

Huang, Hongbiao ^{[1
]}

Zhang, Xiaoyan ^{[1
]}

Li, Shujue ^{[1
]}

Liu, Ningning ^{[1
]}

Lian, Wen ^{[1
]}

McDowell, Emily ^{[2
]}

Zhou, Ping ^{[1
]}

Zhao, Canguo ^{[1
]}

Guo, Haiping ^{[1
]}

Zhang, Change ^{[1
]}

Yang, Changshan ^{[1
]}

Wen, Guangmei ^{[1
]}

Dong, Xiaoxian ^{[1
]}

Lu, Li ^{[1
]}

Ma, Ningfang ^{[1
]}

Dong, Weihua ^{[1
]}

Dou, Q. Ping ^{[1
,3
,4
]}

Wang, Xuejun ^{[1
,2
]}

Liu, Jinbao ^{[1
]}

机构：

[1] Guangzhou Med Coll, Dept Pathophysiol, Prot Modificat & Degradat Lab, Guangzhou 510182, Guangdong, Peoples R China

[2] Univ S Dakota, Sanford Sch Med, Div Basic Biomed Sci, Vermillion, SD 57069 USA

[3] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Prevent Program, Detroit, MI 48201 USA

[4] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA

来源：

CELL RESEARCH | 2010年 / 20卷 / 12期

基金：

中国国家自然科学基金; 国家高技术研究发展计划(863计划);

关键词：

ATP; proteasome; regulation; apoptosis; IN-VIVO; 20S PROTEASOME; INHIBITION; SYSTEM; DEGRADATION; APOPTOSIS; PATHWAY; DIAPHRAGM; NECROSIS; DISEASE;

D O I：

10.1038/cr.2010.123

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Intracellular protein degradation by the ubiquitin-proteasome system is ATP dependent, and the optimal ATP concentration to activate proteasome function in vitro is similar to 100 mu M. Intracellular ATP levels are generally in the low millimolar range, but ATP at a level within this range was shown to inhibit proteasome peptidase activities in vitro. Here, we report new evidence that supports a hypothesis that intracellular ATP at the physiological levels bidirectionally regulates 26S proteasome proteolytic function in the cell. First, we confirmed that ATP exerted bidirectional regulation on the 26S proteasome in vitro, with the optimal ATP concentration (between 50 and 100 mu M) stimulating proteasome chymotrypsin-like activities. Second, we found that manipulating intracellular ATP levels also led to bidirectional changes in the levels of proteasome-specific protein substrates in cultured cells. Finally, measures to increase intracellular ATP enhanced, while decreasing intracellular ATP attenuated the ability of proteasome inhibition to induce cell death. These data strongly suggest that endogenous ATP within the physiological concentration range can exert a negative impact on proteasome activities, allowing the cell to rapidly upregulate proteasome activity on ATP reduction under stress conditions.

引用

页码：1372 / 1385

页数：14

共 43 条

[1] 20S proteasomal degradation of ornithine decarboxylase is regulated by NQ01 [J].