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Identification of Human UMP/CMP Kinase 1 as Doxorubicin Binding Target Using Protein Microarray. 2017

Shuxian Chen, and Xu Wang, and Xianghui Ye, and Donghui Ma, and Caiwei Chen, and Junlong Cai, and Yongfeng Fu, and Xunjia Cheng, and Yun Chen, and Xiaohai Gong, and Jian Jin
1 School of Pharmaceutical Science, Jiangnan University, Wuxi, Jiangsu, China.

Doxorubicin (DOX) is a leading anthracycline drug with exceptional efficacy; however, little is known about the molecular mechanisms of its side effects, which include heart muscle damage, noncancerous cell death, and drug resistance. A total of 17,950 human proteins expressed in HEK293 cells were screened and yielded 14 hits. Competitive and binding experiments further verified the binding of DOX to UMP/CMP kinase 1 (CMPK1), and microscale thermophoresis showed that DOX binds to CMPK1 with a Kd of 1216 nM. In addition, we observed that the binding of DOX to CMPK1 activated the phosphorylation of CMP, dCMP, and UMP. A significant activation was observed at the concentration of 30 µM DOX and reached plateau at the concentration of DOX 30 µM, 150 µM, and 100 µM, respectively. DOX would add up stimulation of CMPK1 by DTT and overcome inhibition of CMPK1 by NaF, EDTA. In summary, we showed that DOX might bind to the nonactive site of CMPK1 and regulate its activity with magnesium.

UI MeSH Term Description Entries
D009703 Nucleoside-Phosphate Kinase An enzyme that catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside monophosphate, e.g., UMP, to form ADP and UDP. Many nucleoside monophosphates can act as acceptor while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.4. Nucleoside Monophosphate Kinases,Kinase, Nucleoside-Phosphate,Kinases, Nucleoside Monophosphate,Monophosphate Kinases, Nucleoside,Nucleoside Phosphate Kinase
D004317 Doxorubicin Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN. Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D027362 Organic Anion Transport Protein 1 A polyspecific transporter for organic cations found primarily in the kidney. It mediates the coupled exchange of alpha-ketoglutarate with organic ions such as P-AMINOHIPPURIC ACID. OAT1 Protein,PAH Transporter,Renal PAN transporter,SLC22A6 Transporter,Solute Carrier Family 22 (Organic Anion Transporter), Member 6,p-Aminohippurate Transporter,PAN transporter, Renal,Transporter, SLC22A6,Transporter, p-Aminohippurate,p Aminohippurate Transporter
D040081 Protein Array Analysis Ligand-binding assays that measure protein-protein, protein-small molecule, or protein-nucleic acid interactions using a very large set of capturing molecules, i.e., those attached separately on a solid support, to measure the presence or interaction of target molecules in the sample. Protein Chips,Protein Microarrays,Protein Microchips,Protein Profiling Chips,Protein Array Assay,Protein Arrays,Protein Biochips,Protein Microarray Analysis,Protein Microarray Assay,Protein Profiling Microarrays,ProteinChip,Analyses, Protein Array,Analyses, Protein Microarray,Analysis, Protein Array,Analysis, Protein Microarray,Array Analyses, Protein,Array Analysis, Protein,Array Assay, Protein,Array Assays, Protein,Array, Protein,Arrays, Protein,Assay, Protein Array,Assay, Protein Microarray,Assays, Protein Array,Assays, Protein Microarray,Biochip, Protein,Biochips, Protein,Chip, Protein,Chip, Protein Profiling,Chips, Protein,Chips, Protein Profiling,Microarray Analyses, Protein,Microarray Analysis, Protein,Microarray Assay, Protein,Microarray Assays, Protein,Microarray, Protein,Microarray, Protein Profiling,Microarrays, Protein,Microarrays, Protein Profiling,Microchip, Protein,Microchips, Protein,Profiling Chip, Protein,Profiling Chips, Protein,Profiling Microarray, Protein,Profiling Microarrays, Protein,Protein Array,Protein Array Analyses,Protein Array Assays,Protein Biochip,Protein Chip,Protein Microarray,Protein Microarray Analyses,Protein Microarray Assays,Protein Microchip,Protein Profiling Chip,Protein Profiling Microarray,ProteinChips

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