title: Function of Nup98 subtypes and their fusion proteins, Nup98-TopIIβ and Nup98-SETBP1 in nuclear-cytoplasmic transport.
abstract: Nup98 is a component of the nuclear pore complex. The nup98-fusion genes derived by chromosome translocations are involved in hematopoietic malignancies. Here, we investigated the functions of Nup98 isoforms and two unexamined Nup98-fusion proteins, Nup98-TopIIβ and Nup98-SETBP1. We first demonstrated that two Nup98 isoforms are expressed in various mouse tissues and similarly localized in the nucleus and the nuclear envelope. We also showed that Nup98-TopIIβ and Nup98-SETBP1 are localized in the nucleus and partially co-localized with full-length Nup98 and a nuclear export receptor XPO1. We demonstrated that Nup98-TopIIβ and Nup98-SETBP1 negatively regulate the XPO1-mediated protein export. Our results will contribute to the understanding of the molecular mechanism by which the Nup98-fusion proteins induce tumorigenesis.
authors.affiliation: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan. Electronic address: ssaito@md.tsukuba.ac.jp.
authors.forename: Shoko
authors.initials: S
authors.lastname: Saito
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yokokawa
authors.affiliation: School of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Gemmei
authors.initials: G
authors.lastname: Iizuka
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Sadik
authors.initials: S
authors.lastname: Cigdem
authors.affiliation: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Okuwaki
authors.affiliation: University of Tsukuba, Tsukuba, Japan. Electronic address: knagata@md.tsukuba.ac.jp.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nagata
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013045:Species Specificity
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D011993:Recombinant Fusion Proteins; C425066:SETBP1 protein, human; C574812:Setbp1 protein, mouse; C093350:nuclear pore complex protein 98; D004250:DNA Topoisomerases, Type II
keywords: Leukemia; Nuclear export; Nuclear localization signal; Nucleoporin; Nup98; XPO1/CRM1