Kaposi's sarcoma-associated herpesvirus-encoded LANA positively affects on ubiquitylation of p53.
We established a series of stable transfectants expressing wild-type and three mutant LANA; amino terminus, carboxyl terminus and amino terminus plus DNA binding domain, as a new strategy to assess systematically the interactions and binding domains with cellular proteins. Using the system, we reported that LANA specifically bound to p53 via DNA binding domain. As for LANA function in the regulation of p53 through the interaction, we showed that polyubiquitylation of p53 in the presence of LANA was obviously increased. LANA also associated with Cullin 5 and Rbx1, active subunit of E3 ubiquitin ligase complex. Taken together, the present study suggests that LANA induce enhancement of p53 ubiquitylation and degradation into proteasome, consequently contributing to latent persistence.
Research Team for Viral Diseases, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856, Japan. tohru_suzuki@affrc.go.jp
Tohru
T
Suzuki
Tomoyasu
T
Isobe
Masatoshi
M
Kitagawa
Keiji
K
Ueda
D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D044842:Cullin Proteins / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
D000956:Antigens, Viral; C496871:CUL5 protein, human; D002352:Carrier Proteins; D044842:Cullin Proteins; D009687:Nuclear Proteins; C479529:RBX1 protein, human; D016159:Tumor Suppressor Protein p53; C109540:latency-associated nuclear antigen; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex