Human Herpesvirus-6 U14 Induces Cell-Cycle Arrest in G2/M Phase by Associating with a Cellular Protein, EDD.
The human herpesvirus-6 (HHV-6) infection induces cell-cycle arrest. In this study, we found that the HHV-6-encoded U14 protein induced cell-cycle arrest at G2/M phase via an association with the cellular protein EDD, a mediator of DNA-damage signal transduction. In the early phase of HHV-6 infection, U14 colocalized with EDD dots in the nucleus, and similar colocalization was also observed in cells transfected with a U14 expression vector. When the carboxyl-terminal region of U14 was deleted, no association of U14 and EDD was observed, and the percentage of cells in G2/M decreased relative to that in cells expressing wild-type U14, indicating that the C-terminal region of U14 and the U14-EDD association are critical for the cell-cycle arrest induced by U14. These results indicate that U14 is a G2/M checkpoint regulator encoded by HHV-6.
Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, 6500017, Japan.
Junko
J
Mori
Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, 6500017, Japan.
Akiko
A
Kawabata
Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, 6500017, Japan; Department of Immunology, Nanjing Medical University, Nanjing, 210029, China.
Huamin
H
Tang
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 6028566, Japan.
Kenjiro
K
Tadagaki
Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 5650871, Japan.
Hiroyuki
H
Mizuguchi
Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, 1738610, Japan.
Kazumichi
K
Kuroda
Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, 6500017, Japan; Laboratory of Virology and Vaccinology, National Institute of Biomedical Innovation, Osaka, 5670085, Japan.
Yasuko
Y
Mori
D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000473:pathology / Q000821:virology; D064447:Checkpoint Kinase 2 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D015654:Herpesvirus 6, Human / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology / Q000821:virology*; D011485:Protein Binding; D015398:Signal Transduction; D013601:T-Lymphocytes; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D014764:Viral Proteins; C117617:UBR5 protein, human; D044767:Ubiquitin-Protein Ligases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human