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

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.
Authors	Xi Liu, Jennifer Hein, Simon C W Richardson, Per H Basse, Tuna Toptan, Patrick S Moore, Ole V Gjoerup, Yuan Chang
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 286 Issue 19 Pg. 17079-90 (May 13 2011) ISSN: 1083-351X [Electronic] United States
PMID	21454559 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Antigens, Polyomavirus Transforming Autophagy-Related Proteins Intracellular Signaling Peptides and Proteins Retinoblastoma Protein VPS39 protein, human Vesicular Transport Proteins
Topics	Antigens, Polyomavirus Transforming (chemistry) Autophagy-Related Proteins Cell Line, Tumor Cell Nucleus (metabolism) Cytoplasm (metabolism) Exocytosis Humans Intracellular Signaling Peptides and Proteins (chemistry, metabolism) Lysosomes (metabolism) Mass Spectrometry Merkel Cells (virology) Models, Biological Protein Binding Protein Transport Retinoblastoma Protein (metabolism) Transfection Vesicular Transport Proteins (chemistry, metabolism) Virus Replication

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