Regulation of bovine papillomavirus replicative helicase e1 by the ubiquitin-proteasome pathway.
J Virol
; 76(22): 11350-8, 2002 Nov.
Article
en En
| MEDLINE
| ID: mdl-12388695
ABSTRACT
Papillomaviruses maintain their genomes in a relatively constant copy number as stable extrachromosomal plasmids in the nuclei of dividing host cells. The viral initiator of replication, E1, is not detected in papillomavirus-infected cells. Here, we present evidence that E1 encoded by bovine papillomavirus type 1 is an unstable protein that is degraded through the ubiquitin-proteasome pathway. In a cell-free system derived from Xenopus egg extracts, E1 degradation is regulated by both cyclin E/Cdk2 binding and E1 replication activity. Free E1 is readily ubiquitinated and degraded by the proteasome, while it becomes resistant to this degradation pathway when bound to cyclin E/Cdk2 complexes before the start of DNA synthesis. This stabilization is reversed in a process involving E1-dependent replication activity. In transiently transfected cells, E1 is also polyubiquitinated and accumulates when proteasome activity is inhibited. Thus, the establishment and maintenance of a stable number of papillomavirus genomes in latently infected cells are in part a function of regulated ubiquitin-mediated degradation of E1.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Virales
/
Cisteína Endopeptidasas
/
Regulación Viral de la Expresión Génica
/
ADN Helicasas
/
Ubiquitina
/
Quinasas CDC2-CDC28
/
Proteínas de Unión al ADN
/
Papillomavirus Bovino 1
/
Complejos Multienzimáticos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Virol
Año:
2002
Tipo del documento:
Article
País de afiliación:
Francia