DDIAS suppresses TRAIL-mediated apoptosis by inhibiting DISC formation and destabilizing caspase-8 in cancer cells

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dc.contributor.authorJoo-Young Im-
dc.contributor.authorBo Kyung Kim-
dc.contributor.authorJi Young Lee-
dc.contributor.authorSeung Ho Park-
dc.contributor.authorHyun Seung Ban-
dc.contributor.authorK E Jung-
dc.contributor.authorMi Sun Won-
dc.date.accessioned2018-04-19T05:19:10Z-
dc.date.available2018-04-19T05:19:10Z-
dc.date.issued2018-
dc.identifier.issn0950-9232-
dc.identifier.uri10.1038/s41388-017-0025-yko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/17777-
dc.description.abstractDNA damage-induced apoptosis suppressor (DDIAS) has an anti-apoptotic function during DNA damage in lung cancer. However, the anti-apoptotic mechanism of DDIAS in cancer cells under other conditions has not been reported. We report here that DDIAS protects cancer cells from tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by two distinct mechanisms in non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC) cells. DDIAS depletion sensitized NSCLC and HCC cells to TRAIL-mediated apoptosis, an effect that was abrogated by pharmacological or genetic inhibition of caspase-8 and was independent of caspase-9, p53, or mitogen-activated protein kinase signaling. Interestingly, we found that the N terminus of DDIAS interacted with the death effector domain of Fas-associated protein death domain (FADD) and prevented its recruitment to the death-inducing signaling complex (DISC), thereby blocking caspase-8 activation. DDIAS knockdown also suppressed epidermal growth factor-induced phosphorylation of p90 ribosomal S6 kinase (RSK) 2 and stabilized caspase-8 by preventing its ubiquitination and proteasomal degradation. This effect was abolished by RSK2 overexpression. Taken together, DDIAS has dual functions in inhibiting DISC formation as well as in destabilizing caspase-8, thereby suppressing TRAIL-mediated apoptosis of cancer cells. Thus, we suggest that DDIAS can serve as an effective therapeutic target in the treatment of NSCLC and HCC-
dc.publisherSpringer-Nature Pub Group-
dc.titleDDIAS suppresses TRAIL-mediated apoptosis by inhibiting DISC formation and destabilizing caspase-8 in cancer cells-
dc.title.alternativeDDIAS suppresses TRAIL-mediated apoptosis by inhibiting DISC formation and destabilizing caspase-8 in cancer cells-
dc.typeArticle-
dc.citation.titleOncogene-
dc.citation.number0-
dc.citation.endPage1262-
dc.citation.startPage1251-
dc.citation.volume37-
dc.contributor.affiliatedAuthorJoo-Young Im-
dc.contributor.affiliatedAuthorBo Kyung Kim-
dc.contributor.affiliatedAuthorJi Young Lee-
dc.contributor.affiliatedAuthorSeung Ho Park-
dc.contributor.affiliatedAuthorHyun Seung Ban-
dc.contributor.affiliatedAuthorMi Sun Won-
dc.contributor.alternativeName임주영-
dc.contributor.alternativeName김보경-
dc.contributor.alternativeName이지영-
dc.contributor.alternativeName박승호-
dc.contributor.alternativeName반현승-
dc.contributor.alternativeName정경은-
dc.contributor.alternativeName원미선-
dc.identifier.bibliographicCitationOncogene, vol. 37, pp. 1251-1262-
dc.identifier.doi10.1038/s41388-017-0025-y-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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