ERK1/2-mediated Cytoplasmic Accumulation of hnRNPK Antagonizes TRAIL-induced Apoptosis through Upregulation of XIAP in H1299 Cells.
- Author:
Wen Si HUANG
1
;
Feng Mei XU
1
;
Qing Zhong ZENG
1
;
Xiao Hui LIU
1
;
Xue Juan GAO
1
;
Lang Xia LIU
1
Author Information
- Publication Type:Journal Article
- Keywords: Apoptosis; ERK1/2; TRAIL; hnRNPK
- MeSH: Apoptosis; physiology; Cell Line, Tumor; Gene Expression Regulation; physiology; Heterogeneous-Nuclear Ribonucleoprotein K; genetics; metabolism; Humans; Mitogen-Activated Protein Kinase 1; genetics; metabolism; Mitogen-Activated Protein Kinase 3; genetics; metabolism; TNF-Related Apoptosis-Inducing Ligand; genetics; metabolism; Up-Regulation; physiology; X-Linked Inhibitor of Apoptosis Protein; genetics; metabolism
- From: Biomedical and Environmental Sciences 2017;30(7):473-481
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETumor 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.
METHODSNuclear 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.
RESULTSPreviously, 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.
CONCLUSIONTaken together, these results give new insights into the understanding of the molecular mechanism associated with TRAIL resistance in lung adenocarcinoma.
