https://scholars.lib.ntu.edu.tw/handle/123456789/545286
標題: | C-FLIP is a target of the E3 ligase deltex1 in gastric cancer | 作者: | Hsu T.-S. Mo S.-T. PING-NING HSU Lai M.-Z. |
公開日期: | 2018 | 出版社: | Nature Publishing Group | 卷: | 9 | 期: | 2 | 起(迄)頁: | 135 | 來源出版物: | Cell Death and Disease | 摘要: | The ubiquitin E3 ligase DELTEX1 (DTX1) is specifically downregulated in gastric cancer tissues, and expression of DTX1 is linked to better prognoses and survival in gastric cancer. Cellular FLICE inhibitory protein (c-FLIP) is known for its pivotal role in the resistance of cancer cells to death receptor-induced cell death. Here, we show that DTX1 is an E3 ligase for c-FLIP in gastric cancer cells. DTX1 promoted c-FLIP downregulation. Overexpression of DTX1 sensitized gastric cancer cells to TRAIL-induced apoptosis, whereas DTX1-knockdown attenuated apoptosis induction. DTX1 binds c-FLIP L and directs it into the endosome-lysosomal pathway for proteasome-independent degradation. Moreover, induction of DTX1 in AGS cells by geldanamycin conferred susceptibility of those cells to TRAIL-induced apoptosis. Our results reveal a tumor-suppressive role for DTX1 and suggest a new approach to increasing TRAIL efficacy by raising DTX1 levels in gastric cancer therapy. DTX1 also enhanced c-FLIP degradation and FasL-induced and TRAIL-induced apoptosis in T cells, suggesting that DTX1 constitutes one of the physiological mechanisms regulating c-FLIP stability. ? 2018 The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85041222061&doi=10.1038%2fs41419-017-0165-6&partnerID=40&md5=1c85dca1b9a5be6cb3518fb9f9cf2da1 https://scholars.lib.ntu.edu.tw/handle/123456789/545286 https://www.nature.com/articles/s41419-017-0165-6 |
ISSN: | 2041-4889 | DOI: | 10.1038/s41419-017-0165-6 | SDG/關鍵字: | FLICE inhibitory protein; geldanamycin; protein deltex1; tumor necrosis factor related apoptosis inducing ligand; ubiquitin protein ligase E3; unclassified drug; benzoquinone derivative; DTX1 protein, human; Fas ligand; FLICE inhibitory protein; macrocyclic lactam; protein binding; tumor necrosis factor related apoptosis inducing ligand; ubiquitin protein ligase; AGS cell line; apoptosis; Article; controlled study; down regulation; endosome; gene overexpression; human; human cell; lysosome; priority journal; protein degradation; protein function; protein protein interaction; protein stability; protein targeting; signal transduction; stomach cancer; disease exacerbation; disease free survival; drug effect; metabolism; pathology; stomach tumor; tumor cell line; Apoptosis; Benzoquinones; CASP8 and FADD-Like Apoptosis Regulating Protein; Cell Line, Tumor; Disease Progression; Disease-Free Survival; Down-Regulation; Endosomes; Fas Ligand Protein; Humans; Lactams, Macrocyclic; Lysosomes; Protein Binding; Proteolysis; Stomach Neoplasms; TNF-Related Apoptosis-Inducing Ligand; Ubiquitin-Protein Ligases |
顯示於: | 醫學系 |
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