Efficient parvovirus replication requires CRL4Cdt2-targeted depletion of p21 to prevent its inhibitory interaction with PCNA.
PLoS Pathog
; 10(4): e1004055, 2014 Apr.
Article
en En
| MEDLINE
| ID: mdl-24699724
ABSTRACT
Infection by the autonomous parvovirus minute virus of mice (MVM) induces a vigorous DNA damage response in host cells which it utilizes for its efficient replication. Although p53 remains activated, p21 protein levels remain low throughout the course of infection. We show here that efficient MVM replication required the targeting for degradation of p21 during this time by the CRL4Cdt2 E3-ubiquitin ligase which became re-localized to MVM replication centers. PCNA provides a molecular platform for substrate recognition by the CRL4Cdt2 E3-ubiquitin ligase and p21 targeting during MVM infection required its interaction both with Cdt2 and PCNA. PCNA is also an important co-factor for MVM replication which can be antagonized by p21 in vitro. Expression of a stable p21 mutant that retained interaction with PCNA inhibited MVM replication, while a stable p21 mutant which lacked this interaction did not. Thus, while interaction with PCNA was important for targeting p21 to the CRL4Cdt2 ligase re-localized to MVM replication centers, efficient viral replication required subsequent depletion of p21 to abrogate its inhibition of PCNA.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Replicación Viral
/
Proteínas Nucleares
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Infecciones por Parvoviridae
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Antígeno Nuclear de Célula en Proliferación
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Ubiquitina-Proteína Ligasas
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina
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Virus Diminuto del Ratón
Límite:
Animals
/
Humans
Idioma:
En
Revista:
PLoS Pathog
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos