期刊论文详细信息
International Journal of Molecular Sciences
Identification of Arsenic Direct-Binding Proteins in Acute Promyelocytic Leukaemia Cells
Tao Zhang2  Haojie Lu3  Weijun Li1  Ronggui Hu1  Zi Chen4 
[1] State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China;Department of Laboratory Medicine, Huashan Hospital, Fudan University, 12 Central Urumqi Road, Shanghai 200040, China;Shanghai Cancer Center and Key Laboratory of Glycoconjugates Research Ministry of Public Health, Fudan University, Shanghai 200032, China;;Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, China
关键词: arsenic-binding protein;    arsenic-biotin;    acute promyelocytic leukaemia;    LC-MS/MS;    pyruvate kinase M2;   
DOI  :  10.3390/ijms161125994
来源: mdpi
PDF
【 摘 要 】

The identification of arsenic direct-binding proteins is essential for determining the mechanism by which arsenic trioxide achieves its chemotherapeutic effects. At least two cysteines close together in the amino acid sequence are crucial to the binding of arsenic and essential to the identification of arsenic-binding proteins. In the present study, arsenic binding proteins were pulled down with streptavidin and identified using a liquid chromatograph-mass spectrometer (LC-MS/MS). More than 40 arsenic-binding proteins were separated, and redox-related proteins, glutathione S-transferase P1 (GSTP1), heat shock 70 kDa protein 9 (HSPA9) and pyruvate kinase M2 (PKM2), were further studied using binding assays in vitro. Notably, PKM2 has a high affinity for arsenic. In contrast to PKM2, GSTP1and HSPA9 did not combine with arsenic directly in vitro. These observations suggest that arsenic-mediated acute promyelocytic leukaemia (APL) suppressive effects involve PKM2. In summary, we identified several arsenic binding proteins in APL cells and investigated the therapeutic mechanisms of arsenic trioxide for APL. Further investigation into specific signal pathways by which PKM2 mediates APL developments may lead to a better understanding of arsenic effects on APL.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.

【 预 览 】
附件列表
Files Size Format View
RO202003190003625ZK.pdf 1265KB PDF download
  文献评价指标  
  下载次数:12次 浏览次数:4次