A20 targets caspase-8 and FADD to protect HTLV-I-infected cells
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 l...
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| Veröffentlicht in: | Leukemia 2016-03, Vol.30 (3), p.716-727 |
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| creator | Saitoh, Y Hamano, A Mochida, K Kakeya, A Uno, M Tsuruyama, E Ichikawa, H Tokunaga, F Utsunomiya, A Watanabe, T Yamaoka, S |
| description | 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. |
| doi_str_mv | 10.1038/leu.2015.267 |
| format | Article |
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Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saitoh, Y</au><au>Hamano, A</au><au>Mochida, K</au><au>Kakeya, A</au><au>Uno, M</au><au>Tsuruyama, E</au><au>Ichikawa, H</au><au>Tokunaga, F</au><au>Utsunomiya, A</au><au>Watanabe, T</au><au>Yamaoka, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A20 targets caspase-8 and FADD to protect HTLV-I-infected cells</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2016-03-01</date><risdate>2016</risdate><volume>30</volume><issue>3</issue><spage>716</spage><epage>727</epage><pages>716-727</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26437781</pmid><doi>10.1038/leu.2015.267</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_proquest_miscellaneous_1773832477 |
| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | 13/2 13/95 38/109 38/89 631/67/395 631/80/82/23 631/80/86 64/60 82/80 Adult Animal models Animals Cancer Research Care and treatment Caspase 3 - genetics Caspase 3 - metabolism Caspase 7 - genetics Caspase 7 - metabolism Caspase 8 - genetics Caspase 8 - metabolism Caspase-8 Cell activation Cell Death Cell Line Cell lineage Cellular proteins Critical Care Medicine Depletion Development and progression DNA-Binding Proteins - antagonists & inhibitors DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Domains FADD protein Fas-Associated Death Domain Protein - genetics Fas-Associated Death Domain Protein - metabolism Female Gene Expression Regulation, Leukemic Genetic aspects Genetic Vectors Health aspects HEK293 Cells Hematology Host-Pathogen Interactions HTLV infections Human T-lymphotropic virus 1 Human T-lymphotropic virus 1 - genetics Human T-lymphotropic virus 1 - pathogenicity Humans Intensive Internal Medicine Intracellular Signaling Peptides and Proteins - antagonists & inhibitors Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Lentivirus - genetics Leukemia Leukemia-Lymphoma, Adult T-Cell - genetics Leukemia-Lymphoma, Adult T-Cell - metabolism Leukemia-Lymphoma, Adult T-Cell - pathology Leukemia-Lymphoma, Adult T-Cell - virology Lymphocytes B Lymphocytes T Lymphoma Medicine Medicine & Public Health Methods Mice Mice, Inbred NOD Molecular targeted therapy Mutation Neoplasm Transplantation Nuclear Proteins - antagonists & inhibitors Nuclear Proteins - genetics Nuclear Proteins - metabolism Oncology original-article Retroviridae RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Signal Transduction Survival Therapeutic targets Tumor Burden Tumor Necrosis Factor alpha-Induced Protein 3 Tumorigenicity Ubiquitin Ubiquitin-proteasome system Viruses Xenografts Xenotransplantation Zinc finger proteins |
| title | A20 targets caspase-8 and FADD to protect HTLV-I-infected cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-12T06%3A41%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A20%20targets%20caspase-8%20and%20FADD%20to%20protect%20HTLV-I-infected%20cells&rft.jtitle=Leukemia&rft.au=Saitoh,%20Y&rft.date=2016-03-01&rft.volume=30&rft.issue=3&rft.spage=716&rft.epage=727&rft.pages=716-727&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/leu.2015.267&rft_dat=%3Cgale_proqu%3EA447637125%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1769607209&rft_id=info:pmid/26437781&rft_galeid=A447637125&rfr_iscdi=true |