The DR6 protein from human herpesvirus-6B induces p53-independent cell cycle arrest in G2/M

Mariane H Schleimann, Søren Hoberg, Aida S Hansen, Bettina Bundgaard, Christoffer T Witt, Emil Kofod-Olsen, Per Höllsberg

Research output: Contribution to journalJournal articleResearchpeer-review

10 Citations (Scopus)

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.

Original languageEnglish
JournalVirology
Volume452-453
Pages (from-to)254-63
Number of pages10
ISSN0042-6822
DOIs
Publication statusPublished - Mar 2014
Externally publishedYes

Keywords

  • Amino Acid Motifs
  • Cell Proliferation
  • Cyclin B1
  • G2 Phase Cell Cycle Checkpoints
  • Herpesvirus 6, Human
  • Humans
  • M Phase Cell Cycle Checkpoints
  • Roseolovirus Infections
  • Tumor Suppressor Protein p53
  • Viral Proteins

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