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.
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