title: HTLV-1 Tax oncoprotein stimulates ROS production and apoptosis in T cells by interacting with USP10.
abstract: Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL), and the viral oncoprotein Tax plays key roles in the immortalization of human T cells, lifelong persistent infection, and leukemogenesis. We herein identify the ubiquitin-specific protease 10 (USP10) as a Tax-interactor in HTLV-1-infected T cells. USP10 is an antistress factor against various environmental stresses, including viral infections and oxidative stress. On exposure to arsenic, an oxidative stress inducer, USP10 is recruited into stress granules (SGs), and USP10-containing SGs reduce reactive oxygen species (ROS) production and inhibit ROS-dependent apoptosis. We found that interaction of Tax with USP10 inhibits arsenic-induced SG formation, stimulates ROS production, and augments ROS-dependent apoptosis in HTLV-1-infected T cells. These findings suggest that USP10 is a host factor that inhibits stress-induced ROS production and apoptosis in HTLV-1-infected T cells; however, its activities are attenuated by Tax. A clinical study showed that combination therapy containing arsenic is effective against some forms of ATL. Therefore, these findings may be relevant to chemotherapy against ATL.
authors.affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Masaya
authors.initials: M
authors.lastname: Higuchi
authors.forename: Grace Naswa
authors.initials: GN
authors.lastname: Makokha
authors.forename: Hideaki
authors.initials: H
authors.lastname: Matsuki
authors.forename: Manami
authors.initials: M
authors.lastname: Yoshita
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000502:physiology; D018053:Arsenites / Q000494:pharmacology; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D015458:Leukemia, T-Cell / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D018053:Arsenites; D016356:Gene Products, tax; D017382:Reactive Oxygen Species; C431363:USP10 protein, human; C514970:tax protein, Human T-lymphotrophic virus 1; D043222:Ubiquitin Thiolesterase; C015001:arsenite