Identification of Arsenic Direct-Binding Proteins in Acute Promyelocytic Leukaemia Cells.
Int J Mol Sci
; 16(11): 26871-9, 2015 Nov 10.
Article
em En
| MEDLINE
| ID: mdl-26569224
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Óxidos
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Arsenicais
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Hormônios Tireóideos
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Proteínas de Transporte
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Proteínas de Choque Térmico HSP70
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Proteínas Mitocondriais
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Glutationa S-Transferase pi
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Proteínas de Membrana
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Proteínas de Neoplasias
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Antineoplásicos
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China