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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 PublicationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN0027-8424
Volume112Issue:49Pages:15084-15089
AbstractArsenic 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.
SubtypeArticle
KeywordArsenic Trioxide Human Proteome Microarray Glycolysis Hexokinase-2
DOI10.1073/pnas.1521316112
WOS HeadingsScience & Technology
Funding OrganizationNational 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 BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000365989800038
WOS KeywordZINC-FINGER PROTEINS ; ACID COMBINATION THERAPY ; INTERACTION NETWORKS ; MULTIPLE-MYELOMA ; ASCORBIC-ACID ; PHASE-II ; TRIOXIDE ; LEUKEMIA ; CANCER ; GENERATION
Funding OrganizationNational 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
Identifierhttp://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
Affiliation1.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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