Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma.
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.
Nakamura
Tomoyuki
T
Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
Sato
Yuko
Y
Watanabe
Daisuke
D
Ito
Hideki
H
Shimonohara
Nozomi
N
Tsuji
Takahiro
T
Nakajima
Noriko
N
Suzuki
Yoshio
Y
Matsuo
Koma
K
Nakagawa
Hidemi
H
Sata
Tetsutaro
T
Katano
Harutaka
H
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis / Q000378:metabolism*; D015153:Blotting, Western; D015266:Carcinoma, Merkel Cell / Q000821:virology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019913:Nuclear Localization Signals / Q000235:genetics; D016133:Polymerase Chain Reaction; D011120:Polyomavirus / Q000276:immunology / Q000502:physiology*; D027601:Polyomavirus Infections / Q000276:immunology / Q000821:virology*; D011817:Rabbits; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics; D012878:Skin Neoplasms / Q000821:virology*; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology*
D000952:Antigens, Polyomavirus Transforming; D019913:Nuclear Localization Signals