时尚
生物
程序性细胞死亡
白血病
细胞凋亡
死亡域
半胱氨酸蛋白酶
病毒学
半胱氨酸蛋白酶8
癌症研究
免疫学
遗传学
作者
Yasunori Saitoh,Akiko Hamano,Kanako Mochida,A Kakeya,Masaya Uno,Eri Tsuruyama,Hirona Ichikawa,Fuminori Tokunaga,Atae Utsunomiya,Toshiki Watanabe,Yasuhiro Shoji
出处
期刊:Leukemia
[Springer Nature]
日期:2015-10-06
卷期号:30 (3): 716-727
被引量:15
摘要
Adult T-cell leukemia (ATL) arises from a human T-cell leukemia virus type I (HTLV-I)-infected cell and has few therapeutic options. Here, we have uncovered a previously unrecognized role for a ubiquitin-editing enzyme A20 in the survival of HTLV-I-infected cells. Unlike in lymphomas of the B-cell lineage, A20 is abundantly expressed in primary ATL cells without notable mutations. Depletion of A20 in HTLV-I-infected cells resulted in caspase activation, cell death induction and impaired tumorigenicity in mouse xenograft models. Mechanistically, A20 stably interacts with caspase-8 and Fas-associated via death domain (FADD) in HTLV-I-infected cells. Mutational studies revealed that A20 supports the growth of HTLV-I-infected cells independent of its catalytic functions and that the zinc-finger domains are required for the interaction with and regulation of caspases. These results indicate a pivotal role for A20 in the survival of HTLV-I-infected cells and implicate A20 as a potential therapeutic target in ATL.
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