New approach to evaluating the effects of a drug on protein complexes with quantitative proteomics, using the SILAC method and bioinformatic approach.
Biosci Biotechnol Biochem
; 83(11): 2034-2048, 2019 Nov.
Article
em En
| MEDLINE
| ID: mdl-31282289
ABSTRACT
Protein-protein interactions (PPIs) lead the formation of protein complexes that perform biochemical reactions that maintain the living state of the living cell. Although therapeutic drugs should influence the formation of protein complexes in addition to PPI network, the methodology analyzing such influences remain to be developed. Here, we demonstrate that a new approach combining HPLC (high performance liquid chromatography) for separating protein complexes, and the SILAC (stable isotope labeling using amino acids in cell culture) method for relative protein quantification, enable us to identify the protein complexes influenced by a drug. We applied this approach to the analysis of thalidomide action on HepG2 cells, assessed the identified proteins by clustering data analyses, and assigned 135 novel protein complexes affected by the drug. We propose that this approach is applicable to elucidating the mechanisms of actions of other therapeutic drugs on the PPI network, and the formation of protein complexes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Proteômica
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Avaliação Pré-Clínica de Medicamentos
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Mapas de Interação de Proteínas
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Aminoácidos
Limite:
Humans
Idioma:
En
Revista:
Biosci Biotechnol Biochem
Ano de publicação:
2019
Tipo de documento:
Article