ERK1/2-mediated Cytoplasmic Accumulation of hnRNPK Antagonizes TRAIL-induced Apoptosis through Upregulation of XIAP in H1299 Cells / 生物医学与环境科学(英文)
Biomedical and Environmental Sciences
; (12): 473-481, 2017.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-311389
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance greatly limits the clinical therapeutic efficacy of TRAIL. Elucidating the molecular mechanism underlying TRAIL resistance will be fundamental to resolving this problem.</p><p><b>METHODS</b>Nuclear and cytoplasmic protein extraction and immuno?uorescence (IF) assay were used to detect changes in heterogeneous nuclear ribonucleoprotein K (hnRNPK) localization in H1299 cells. The evaluation of cell apoptosis in cells transfected with GFP-hnRNPK, GFP-hnRNPK S284/353A, or GFP-hnRNPK S284/353D mutant was performed using cleaved caspase-3 antibody. The gene expression of XIAP was tested by quantitative RT-PCR.</p><p><b>RESULTS</b>Previously, we reported that hnRNPK antagonized TRAIL-induced apoptosis through inhibition of PKC-mediated GSK3β phosphorylation. In this study, we further demonstrate that TRAIL treatment induces cytoplasmic accumulation of hnRNPK in H1299 cells. The hnRNPK localized in the cytoplasm has a higher capacity to antagonize TRAIL-induced apoptosis. Both ERK1/2 signaling inhibitor U0126 and ERK-phosphoacceptor-site mutant (GFP-hnRNPK S284/353A) diminish cytoplasmic accumulation of hnRNPK induced by TRAIL. Moreover, we show that XIAP is involved in hnRNPK-mediated TRAIL resistance in H1299 cells.</p><p><b>CONCLUSION</b>Taken together, these results give new insights into the understanding of the molecular mechanism associated with TRAIL resistance in lung adenocarcinoma.</p>
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fisiologia
/
Regulação para Cima
/
Regulação da Expressão Gênica
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Apoptose
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Proteína Quinase 1 Ativada por Mitógeno
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Ribonucleoproteínas Nucleares Heterogêneas Grupo K
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Linhagem Celular Tumoral
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Proteína Quinase 3 Ativada por Mitógeno
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Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X
/
Ligante Indutor de Apoptose Relacionado a TNF
Limite:
Humanos
Idioma:
Inglês
Revista:
Biomedical and Environmental Sciences
Ano de publicação:
2017
Tipo de documento:
Artigo