c-FLIP is a target of the E3 ligase deltex1 in gastric cancer

التفاصيل البيبلوغرافية
العنوان:	c-FLIP is a target of the E3 ligase deltex1 in gastric cancer
المؤلفون:	Hsu, Tzu-Sheng, Mo, Shu-Ting, Hsu, Ping-Ning, Lai, Ming-Zong
المصدر:	Cell Death & Disease ; volume 9, issue 2 ; ISSN 2041-4889
بيانات النشر:	Springer Science and Business Media LLC
سنة النشر:	2018
الوصف:	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.
نوع الوثيقة:	article in journal/newspaper
اللغة:	English
DOI:	10.1038/s41419-017-0165-6
الاتاحة:	http://dx.doi.org/10.1038/s41419-017-0165-6 https://www.nature.com/articles/s41419-017-0165-6 https://www.nature.com/articles/s41419-017-0165-6.pdf
Rights:	https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0
رقم الانضمام:	edsbas.7FABAE85
قاعدة البيانات:	BASE

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الوصف
DOI:	10.1038/s41419-017-0165-6