Merkel Cell Polyomavirus Large T Antigen Has Growth-Promoting and Inhibitory Activities

Academic Article

Abstract

  • Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. In at least 80% of all MCC, Merkel cell polyomavirus (MCPyV) DNA has undergone clonal integration into the host cell genome, and most tumors express the MCPyV large and small T antigens. In all cases of MCC reported to date, the integrated MCPyV genome has undergone mutations in the large T antigen. These mutations result in expression of a truncated large T antigen that retains the Rb binding or LXCXE motif but deletes the DNA binding and helicase domains. However, the transforming functions of full-length and truncated MCPyV large T antigen are unknown. We compared the transforming activities of full-length, truncated, and alternatively spliced 57kT forms of MCPyV large T antigen. MCPyV large T antigen could bind to Rb but was unable to bind to p53. Furthermore, MCPyV-truncated large T antigen was more effective than full-length and 57kT large T antigen in promoting the growth of human and mouse fibroblasts. In contrast, expression of the MCPyV large T antigen C-terminal 100 residues could inhibit the growth of several different cell types. These data imply that the deletion of the C terminus of MCPyV large T antigen found in MCC serves not only to disrupt viral replication but also results in the loss of a distinct growth-inhibitory function intrinsic to this region.
  • Authors

  • Cheng, Jingwei
  • Rozenblatt-Rosen, O
  • Paulson, KG
  • Nghiem, P
  • DeCaprio, JA
  • Status

    Publication Date

  • June 1, 2013
  • Has Subject Area

    Published In

    Keywords

  • Amino Acid Motifs Animals Antigens, Polyomavirus Transforming/chemistry/genetics/*metabolism Carcinoma, Merkel Cell/genetics/metabolism/*physiopathology/virology Cell Proliferation Cell Transformation, Neoplastic Growth Substances/chemistry/genetics/*metabolism Humans Merkel cell polyomavirus/chemistry/genetics/*physiology Mice Skin Neoplasms/genetics/metabolism/*physiopathology/virology Tumor Virus Infections/genetics/metabolism/*physiopathology/virology
  • Digital Object Identifier (doi)

    Start Page

  • 6118
  • End Page

  • 6126
  • Volume

  • 87
  • Issue

  • 11