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Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus

Liu, Xi, Hein, Jennifer, Richardson, Simon C. W., Basse, Per H, Toptan, Tuna, Moore, Patrick, Gjoerup, Ole V, Chang, Yuan (2011) Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus. Journal of Biological Chemistry, 286 (19). pp. 17079-17090. ISSN 0021-9258. E-ISSN 1083-351X. (doi:10.1074/jbc.M110.192856) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1074/jbc.M110.192856

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.

Item Type: Article
DOI/Identification number: 10.1074/jbc.M110.192856
Additional information: a. The author made a substantial contribution to the analysis and interpretation of study data. The evidence to support this is seen in the the authors (lead author paper): Richardson, S. C. W., Winistorfer, S. C., Poupon, V., Luzio, J. P. & Piper, R. C. Mammalian Late Vacuole Protein Sorting Orthologues Participate in Early Endosomal Fusion and Interact with the Cytoskeleton. Molecular Biology of the Cell 15, 1197–1210 (2004). b.The author helped draft the output; or critique the output for important intellectual content.; number of additional authors: 7;
Uncontrolled keywords: Exocytosis, Lysosomes, Nucleus, Tumor Viruses, Viral Replication, Merkel Cell Polyomavirus, T Antigen, hVam6p, Nuclear Sequestration, Polyomavirus
Subjects: Q Science
R Medicine > RS Pharmacy and materia medica
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Stewart Brownrigg
Date Deposited: 07 Mar 2014 00:05 UTC
Last Modified: 29 May 2019 12:24 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/40427 (The current URI for this page, for reference purposes)
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