Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6140273 | Virology | 2014 | 10 Pages |
â¢HHV-6B-encoded DR6 protein inhibits cell proliferation.â¢DR6 inhibits host cell DNA synthesis independent of p53.â¢DR6 delays the cell cycle in G2/M.â¢An N-terminal sequence is necessary for DR6 function.â¢DR6 induces cytoplasmic accumulation of cyclin B1.
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.