An essential EBV latent antigen 3C binds Bcl6 for targeted degradation and cell proliferation

The latent ebv nuclear antigen 3c (ebna3c) is required for transformation of primary human b lymphocytes. most mature b-cell malignancies originate from malignant transformation of germinal center (gc) b-cells. the gc reaction appears to have a role in malignant transformation,in which a major player of the gc reaction is bcl6,a key regulator of this process. we now demonstrate that ebna3c contributes to b-cell transformation by targeted degradation of bcl6. we show that ebna3c can physically associate with bcl6. notably,ebna3c expression leads to reduced bcl6 protein levels in a ubiquitin-proteasome dependent manner. further,ebna3c inhibits the transcriptional activity of the bcl6 promoter through interaction with the cellular protein irf4. bcl6 degradation induced by ebna3c rescued the functions of the bcl6-targeted downstream regulatory proteins bcl2 and ccnd1,which resulted in increased proliferation and g1-s transition. these data provide new insights into the function of ebna3c in b-cell transformation during gc reaction,and raises the possibility of developing new targeted therapies against ebv-associated cancers. © 2017 pei et al.