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.
Article
in English
| WPRIM
| ID: wpr-311389
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>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Physiology
/
Up-Regulation
/
Gene Expression Regulation
/
Apoptosis
/
Mitogen-Activated Protein Kinase 1
/
Heterogeneous-Nuclear Ribonucleoprotein K
/
Cell Line, Tumor
/
Mitogen-Activated Protein Kinase 3
/
X-Linked Inhibitor of Apoptosis Protein
/
TNF-Related Apoptosis-Inducing Ligand
Limits:
Humans
Language:
English
Journal:
Biomedical and Environmental Sciences
Year:
2017
Type:
Article
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