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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

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.

Pubmed ID: 21454559 RIS Download

Research resources used in this publication

None found

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: AI078926
  • Agency: NCI NIH HHS, United States
    Id: P30 CA047904
  • Agency: NCI NIH HHS, United States
    Id: R01 CA136363
  • Agency: NCI NIH HHS, United States
    Id: R33 CA120726
  • Agency: NCI NIH HHS, United States
    Id: CA136363
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI078926
  • Agency: NCI NIH HHS, United States
    Id: CA120726

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