Human cytomegalovirus inactivates the G0/G1-APC/C ubiquitin ligase by Cdh1 dissociation.
Cell Cycle
; 4(10): 1435-9, 2005 Oct.
Article
em En
| MEDLINE
| ID: mdl-16138013
The anaphase promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that targets regulators of the cell division cycle for degradation by the 26S proteasome. Discovered as a key regulator of mitosis, the APC/C has more recently been recognized to also play a limiting role in the control of G(0) maintenance, G(1)/S-transition and DNA-replication. Human cytomegalovirus (HCMV) has been shown to interfere with cell cycle regulation at different levels. It can induce an S phase-prone proliferation program in quiescent cells but at the same time this virus directly inhibits competitive cellular DNA replication. Here we show, that human cytomegalovirus (HCMV) inactivates the G(0)/G(1) APC/C rapidly after infection of quiescent fibroblasts, resulting in the untimely stabilization of APC/C substrates. APC/C inactivation is caused by the dissociation of its positive regulator, Cdh1. Surprisingly, this dissociation is independent from known Cdh1 inhibitors, Emi1 and Cyclin A, suggesting that APC/C-Cdh1 inhibition by HCMV is directly caused by a viral protein or an intermediate cellular factor distinct from Emi1 and Cyclin A. Thus, upon infection of quiescent cells HCMV not only activates the E2F-dependent G(1)/S transcription program but also facilitates protein accumulation of APC/C substrates by rapid Cdh1 dissociation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fase de Repouso do Ciclo Celular
/
Fase G1
/
Proteínas de Ciclo Celular
/
Citomegalovirus
/
Complexos Ubiquitina-Proteína Ligase
/
Ubiquitina-Proteína Ligases
Limite:
Humans
Idioma:
En
Revista:
Cell Cycle
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Alemanha