title: The DR6 protein from human herpesvirus-6B induces p53-independent cell cycle arrest in G2/M.
abstract: HHV-6B infection inhibits cell proliferation in G2/M, but no protein has so far been recognized to exert this function. Here we identify the protein product of direct repeat 6, DR6, as an inhibitor of G2/M cell-cycle progression. Transfection of DR6 reduced the total number of cells compared with mock-transfected cells. Lentiviral transduction of DR6 inhibited host cell DNA synthesis in a p53-independent manner, and this inhibition was DR6 dose-dependent. A deletion of 66 amino acids from the N-terminal part of DR6 prevented efficient nuclear translocation and the ability to inhibit DNA synthesis. DR6-induced accumulation of cells in G2/M was accompanied by an enhanced expression of cyclin B1 that accumulated predominantly in the cytoplasm. Pull-down of cyclin B1 brought down pCdk1 with the inactivating phosphorylation at Tyr15. Together, DR6 delays cell cycle with an accumulation of cells in G2/M and thus might be involved in HHV-6B-induced cell-cycle arrest.
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Mariane H
authors.initials: MH
authors.lastname: Schleimann
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Hoberg
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Aida
authors.initials: A
authors.lastname: Solhøj Hansen
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Bettina
authors.initials: B
authors.lastname: Bundgaard
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Christoffer T
authors.initials: CT
authors.lastname: Witt
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Emil
authors.initials: E
authors.lastname: Kofod-Olsen
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark. Electronic address: ph@microbiology.au.dk.
authors.forename: Per
authors.initials: P
authors.lastname: Höllsberg
mesh_terms: D020816:Amino Acid Motifs; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D015654:Herpesvirus 6, Human / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D019349:Roseolovirus Infections / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D056744:Cyclin B1; C000588555:DR6 protein, human herpesvirus 6B; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins
keywords: Direct repeat 6; G2/M arrest; HHV-6; Human herpesvirus 6B; p53