title: 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: Cancer Virology Program, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors: Xi
authors: X
authors: Liu
authors: Jennifer
authors: J
authors: Hein
authors: Simon C W
authors: SC
authors: Richardson
authors: Per H
authors: PH
authors: Basse
authors: Tuna
authors: T
authors: Toptan
authors: Patrick S
authors: PS
authors: Moore
authors: Ole V
authors: OV
authors: Gjoerup
authors: Yuan
authors: Y
authors: Chang
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry*; D000071183:Autophagy-Related Proteins; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D005089:Exocytosis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D013058:Mass Spectrometry; D018862:Merkel Cells / Q000821:virology*; D008954:Models, Biological; D011485:Protein Binding; D021381:Protein Transport; D016160:Retinoblastoma Protein / Q000378:metabolism; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D000952:Antigens, Polyomavirus Transforming; D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016160:Retinoblastoma Protein; C485791:VPS39 protein, human; D033921:Vesicular Transport Proteins