| Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic | |
| Zhang, Hai-nan1,2,3; Yang, Lina1; Ling, Jian-ya4; Czajkowsky, Daniel M.3; Wang, Jing-Fang1; Zhang, Xiao-Wei5; Zhou, Yi-Ming6; Ge, Feng7; Yang, Ming-kun7; Xiong, Qian7; Guo, Shu-Juan1; Le, Huang-Ying1; Wu, Song-Fang1; Yan, Wei1; Liu, Bingya8; Zhu, Heng9,10; Chen, Zhu1,5,11; Tao, Sheng-ce1,2,3,11 | |
| 2015-12-08 | |
| Source Publication | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| ISSN | 0027-8424 |
| Volume | 112Issue:49Pages:15084-15089 |
| Abstract | Arsenic is highly effective for treating acute promyelocytic leukemia (APL) and has shown significant promise against many other tumors. However, although its mechanistic effects in APL are established, its broader anticancer mode of action is not understood. In this study, using a human proteome microarray, we identified 360 proteins that specifically bind arsenic. Among the most highly enriched proteins in this set are those in the glycolysis pathway, including the rate-limiting enzyme in glycolysis, hexokinase-1. Detailed biochemical and metabolomics analyses of the highly homologous hexokinase-2 (HK2), which is overexpressed in many cancers, revealed significant inhibition by arsenic. Furthermore, overexpression of HK2 rescued cells from arsenic-induced apoptosis. Our results thus strongly implicate glycolysis, and HK2 in particular, as a key target of arsenic. Moreover, the arsenic-binding proteins identified in this work are expected to serve as a valuable resource for the development of synergistic antitumor therapeutic strategies. |
| Subtype | Article |
| Keyword | Arsenic Trioxide Human Proteome Microarray Glycolysis Hexokinase-2 |
| DOI | 10.1073/pnas.1521316112 |
| WOS Headings | Science & Technology |
| Funding Organization | National High Technology Research and Development Program of China(2012AA020103 ; National High Technology Research and Development Program of China(2012AA020103 ; National Natural Science Foundation of China(31370813 ; National Natural Science Foundation of China(31370813 ; Key Project Specialized for Infectious Diseases of the Chinese Ministry of Health Grant(2013ZX10003006) ; Key Project Specialized for Infectious Diseases of the Chinese Ministry of Health Grant(2013ZX10003006) ; 2012AA020203) ; 2012AA020203) ; 31370750) ; 31370750) ; National High Technology Research and Development Program of China(2012AA020103 ; National High Technology Research and Development Program of China(2012AA020103 ; National Natural Science Foundation of China(31370813 ; National Natural Science Foundation of China(31370813 ; Key Project Specialized for Infectious Diseases of the Chinese Ministry of Health Grant(2013ZX10003006) ; Key Project Specialized for Infectious Diseases of the Chinese Ministry of Health Grant(2013ZX10003006) ; 2012AA020203) ; 2012AA020203) ; 31370750) ; 31370750) |
| Indexed By | SCI |
| Language | 英语 |
| WOS Research Area | Science & Technology - Other Topics |
| WOS Subject | Multidisciplinary Sciences |
| WOS ID | WOS:000365989800038 |
| WOS Keyword | ZINC-FINGER PROTEINS ; ACID COMBINATION THERAPY ; INTERACTION NETWORKS ; MULTIPLE-MYELOMA ; ASCORBIC-ACID ; PHASE-II ; TRIOXIDE ; LEUKEMIA ; CANCER ; GENERATION |
| Funding Organization | National High Technology Research and Development Program of China(2012AA020103 ; National High Technology Research and Development Program of China(2012AA020103 ; National Natural Science Foundation of China(31370813 ; National Natural Science Foundation of China(31370813 ; Key Project Specialized for Infectious Diseases of the Chinese Ministry of Health Grant(2013ZX10003006) ; Key Project Specialized for Infectious Diseases of the Chinese Ministry of Health Grant(2013ZX10003006) ; 2012AA020203) ; 2012AA020203) ; 31370750) ; 31370750) ; National High Technology Research and Development Program of China(2012AA020103 ; National High Technology Research and Development Program of China(2012AA020103 ; National Natural Science Foundation of China(31370813 ; National Natural Science Foundation of China(31370813 ; Key Project Specialized for Infectious Diseases of the Chinese Ministry of Health Grant(2013ZX10003006) ; Key Project Specialized for Infectious Diseases of the Chinese Ministry of Health Grant(2013ZX10003006) ; 2012AA020203) ; 2012AA020203) ; 31370750) ; 31370750) |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ihb.ac.cn/handle/342005/27449 |
| Collection | 水生生物分子与细胞生物学研究中心_期刊论文 |
| Affiliation | 1.Shanghai Jiao Tong Univ, Shanghai Ctr Syst Biomed, Key Lab Syst Biomed, Minist Educ, Shanghai 200240, Peoples R China 2.State Key Lab Oncogenes & Related Genes, Shanghai 200240, Peoples R China 3.Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200240, Peoples R China 4.Shandong Univ, Sch Life Sci, State Key Lab Microbial Technol, Jinan 250100, Peoples R China 5.Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Ruijin Hosp, Shanghai 200025, Peoples R China 6.Natl Engn Res Ctr Beijing Biochip Technol, Beijing 102206, Peoples R China 7.Chinese Acad Sci, Inst Hydrobiol, Key Lab Algal Biol, Wuhan 430072, Peoples R China 8.Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Gastr Neoplasms, Shanghai Inst Digest Surg,Ruijin Hosp, Shanghai 200025, Peoples R China 9.Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA 10.Johns Hopkins Univ, Sch Med, High Throughput Biol Ctr, Baltimore, MD 21205 USA 11.Collaborat Innovat Ctr Syst Biomed, Shanghai 200240, Peoples R China |
| Recommended Citation GB/T 7714 | Zhang, Hai-nan,Yang, Lina,Ling, Jian-ya,et al. Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2015,112(49):15084-15089. |
| APA | Zhang, Hai-nan.,Yang, Lina.,Ling, Jian-ya.,Czajkowsky, Daniel M..,Wang, Jing-Fang.,...&Tao, Sheng-ce.(2015).Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,112(49),15084-15089. |
| MLA | Zhang, Hai-nan,et al."Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 112.49(2015):15084-15089. |
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