Liu, Xi, Hein, Jennifer, Richardson, Simon C.W. ORCID: 0000-0002-7927-0649, Basse, Per H., Toptan, Tuna, Moore, Patrick S., Gjoerup, Ole V. and Chang, Yuan (2011) Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus. The Journal of Biological Chemistry, 286 (19). pp. 17079-17090. ISSN 0021-9258 (Print), 1083-351X (Online) (doi:https://doi.org/10.1074/jbc.M110.192856)

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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
Additional Information:	[1] First published, JBC Papers in Press, March 16, 2011, DOI 10.1074/jbc.M110.192856. Published in The Journal of Biological Chemistry, 286 (19), May 13, 2011. [2] This research was originally published in The Journal of Biological Chemistry. Xi Liu, Jennifer Hein, Simon C.W. Richardson, Per H. Basse, Tuna Toptan, Patrick S. Moore, Ole V. Gjoerup and Yuan Chang. Merkel Cell Polyomavirus Large T Antigen Disrupts Lysosome Clustering by Translocating Human Vam6p from the Cytoplasm to the Nucleus. The Journal of Biological Chemistry. 2011; 286:17079-17090. © the American Society for Biochemistry and Molecular Biology. [3] Open Access: Author's Choice — Final version full access. Creative Commons Attribution Non-Commercial License applies to Author Choice Articles.
Uncontrolled Keywords:	exocytosis, lysosomes, nucleus, tumor viruses, viral replication, Merkel cell polyomavirus, T Antigen, hVam6p, nuclear sequestration, polyomavirus
Subjects:	Q Science > QP Physiology R Medicine > RM Therapeutics. Pharmacology
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science > School of Science (SCI)
Related URLs:	Publisher Organisation
Last Modified:	06 Nov 2020 11:23
URI:	http://gala.gre.ac.uk/id/eprint/5569

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