| RRC ID |
43305
|
| 著者 |
Ushijima Y, Koshizuka T, Goshima F, Kimura H, Nishiyama Y.
|
| タイトル |
Herpes simplex virus type 2 UL56 interacts with the ubiquitin ligase Nedd4 and increases its ubiquitination.
|
| ジャーナル |
J Virol
|
| Abstract |
The herpes simplex virus UL56 gene is conserved among most members of the Alphaherpesvirinae family and plays a critical role in viral pathogenicity in vivo. The HSV-2 UL56 protein (UL56) is a C-terminally anchored type II membrane protein that is predicted to be inserted into the virion envelope, leaving its N-terminal domain in the tegument. UL56 interacts with KIF1A and UL11. Here we report that UL56 also interacts with the ubiquitin ligase Nedd4 and increases its ubiquitination. Nedd4 was identified as a UL56-interacting protein by a yeast two-hybrid screen. UL56 bound to Nedd4 via its PY motifs. Nedd4 was phosphorylated and degraded in wild-type HSV-2-infected cells but not in cells infected with a UL56-deficient mutant. Ubiquitination assays revealed that UL56 increased ubiquitinated Nedd4, which was actively degraded in infected cells. UL56 also caused a decrease in Nedd4 protein levels and the increased ubiquitination in cotransfected cells. However, UL56 itself was not ubiquitinated, despite its interaction with Nedd4. Based on these findings, we propose that UL56 regulates Nedd4 in HSV-2-infected cells, although deletion of UL56 had no apparent effect on viral growth in vitro.
|
| 巻・号 |
82(11)
|
| ページ |
5220-33
|
| 公開日 |
2008-6-1
|
| DOI |
10.1128/JVI.02515-07
|
| PII |
JVI.02515-07
|
| PMID |
18353951
|
| PMC |
PMC2395212
|
| MeSH |
Amino Acid Motifs
Animals
Cell Line
Chlorocebus aethiops
Gene Expression Regulation, Viral
Herpesvirus 2, Human / chemistry
Herpesvirus 2, Human / genetics
Herpesvirus 2, Human / metabolism*
Humans
Molecular Sequence Data
Phosphorylation
Proteasome Endopeptidase Complex / metabolism
Protein Binding
Sequence Alignment
Sequence Homology, Amino Acid
Ubiquitin-Protein Ligases / metabolism*
Ubiquitination
Viral Proteins / chemistry
Viral Proteins / genetics
Viral Proteins / metabolism*
|
| IF |
4.501
|
| 引用数 |
30
|
|
WOS 分野
|
VIROLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
SK-N-SH(RCB0426)
HEp-2(RCB1889) |
