Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus.
J Biol Chem
; 286(19): 17079-90, 2011 May 13.
Article
em En
| MEDLINE
| ID: mdl-21454559
ABSTRACT
Merkel cell polyomavirus (MCV) has been recently described as the cause for most human Merkel cell carcinomas. MCV is similar to simian virus 40 (SV40) and encodes a nuclear large T (LT) oncoprotein that is usually mutated to eliminate viral replication among tumor-derived MCV. We identified the hVam6p cytoplasmic protein involved in lysosomal processing as a novel interactor with MCV LT but not SV40 LT. hVam6p binds through its clathrin heavy chain homology domain to a unique region of MCV LT adjacent to the retinoblastoma binding site. MCV LT translocates hVam6p to the nucleus, sequestering it from involvement in lysosomal trafficking. A naturally occurring, tumor-derived mutant LT (MCV350) lacking a nuclear localization signal binds hVam6p but fails to inhibit hVam6p-induced lysosomal clustering. MCV has evolved a novel mechanism to target hVam6p that may contribute to viral uncoating or egress through lysosomal processing during virus replication.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Núcleo Celular
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Antígenos Transformantes de Poliomavirus
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Células de Merkel
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Citoplasma
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Proteínas de Transporte Vesicular
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Peptídeos e Proteínas de Sinalização Intracelular
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Lisossomos
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article