Nucleo-cytoplasmic shuttling of high risk human Papillomavirus E2 proteins induces apoptosis.
J Biol Chem
; 280(43): 36088-98, 2005 Oct 28.
Article
em En
| MEDLINE
| ID: mdl-16135518
ABSTRACT
Human Papillomavirus (HPV) E2 proteins are the major viral regulators of transcription and replication during the viral life cycle. In addition to these conserved functions, we show that E2 proteins from high risk HPV types 16 and 18, which are associated with cervical cancer, can induce apoptosis. In contrast, E2 proteins from low risk HPV types 6 and 11, which are associated with benign lesions, do not cause cell death. We show that the ability to induce apoptosis is linked to the intracellular localization of the respective E2 proteins rather than to inherent properties of the proteins. Although low risk HPV E2 proteins remain strictly nuclear, high risk HPV E2 proteins are present in both the nucleus and the cytoplasm of expressing cells due to exportin-1 receptor (CRM1)-dependent nucleo-cytoplasmic shuttling. Induction of apoptosis is caused by accumulation of E2 in the cytoplasm and involves caspase 8 activation. We speculate that disruption of the E2 gene during viral genome integration in cervical carcinoma provides a means to avoid E2-induced apoptosis and allow initiation of carcinogenesis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Papillomaviridae
/
Proteínas Virais
/
Núcleo Celular
/
Neoplasias do Colo do Útero
/
Proteínas Oncogênicas Virais
/
Apoptose
/
Receptores Citoplasmáticos e Nucleares
/
Citoplasma
/
Carioferinas
/
Proteínas de Ligação a DNA
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
França