Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma.

Abstract

To clarify whether mutations in the large T gene encoded by Merkel cell polyomavirus affect the expression and function of large T antigen in Merkel cell carcinoma cases, we investigated the expression of large T antigen in vitro and in vivo. Immunohistochemistry using a rabbit polyclonal antibody revealed that large T antigen was expressed in the nuclei of Merkel cell carcinoma cells with Merkel cell polyomavirus infection. Deletion mutant analyses identified an Arg-Lys-Arg-Lys sequence (amino acids 277-280) as a nuclear localization signal in large T antigen. Sequence analyses revealed that there were no mutations in the nuclear localization signal in any of the eleven Merkel cell polyomavirus strains examined. Furthermore, stop codons were not observed in the upstream of the nuclear localization signal in any of the Merkel cell carcinoma cases examined. These data suggest that the nuclear localization signal is highly conserved and functional in Merkel cell carcinoma cases.

• Authors: Tomoyuki Nakamura, Yuko Sato, Daisuke Watanabe, Hideki Ito, Nozomi Shimonohara, Takahiro Tsuji, Noriko Nakajima, Yoshio Suzuki, Koma Matsuo, Hidemi Nakagawa, Tetsutaro Sata, Harutaka Katano
• Journal: Virology (Virology) Vol. 398 Issue 2 Pg. 273-9 (Mar 15 2010) ISSN: 1096-0341 [Electronic] United States
• PMID: 20074767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Polyomavirus Transforming
• Nuclear Localization Signals

Topics

• Animals
• Antigens, Polyomavirus Transforming (biosynthesis, metabolism)
• Blotting, Western
• Carcinoma, Merkel Cell (virology)
• Cell Line
• Cell Nucleus (metabolism)
• Gene Expression Regulation, Viral (genetics, physiology)
• Molecular Sequence Data
• Mutagenesis, Site-Directed
• Nuclear Localization Signals (genetics)
• Polymerase Chain Reaction
• Polyomavirus (immunology, physiology)
• Polyomavirus Infections (immunology, virology)
• Rabbits
• Sequence Alignment
• Sequence Deletion (genetics)
• Skin Neoplasms (virology)
• Tumor Virus Infections (immunology, virology)