Plays an essential role for the activation and immortalization of human B-cells. Represses transcription of viral promoters TP1 and Cp through interaction with host RBPJ, and inhibits EBNA2-mediated activation of these promoters. Since Cp is the promoter for all EBNA mRNAs, EBNA6 probably contributes to a negative autoregulatory control loop. Alternatively, EBNA6 also regulates the transcription of the EBV oncogene LMP1 in a cell cycle-dependent manner. Modulates the activity of several host proteins involved in cell cycle regulation including host cyclin A, MYC, RB, p21 and p27 mainly through binding to the host SCF(SKP2) complex. Inhibits the promoter of host H2AX and targets H2AX to proteasomal degradation in order to promote latency and cell proliferation. Interacts with host CTPB1; this interaction seems important for EBNA6-mediated transcriptional repression. Interacts with host MYC; this interaction enhances MYC stability. Interacts (via N-terminus) with host RBPJ. Interacts (via N-terminus) with host histone H2AX; this interaction facilitates H2AX proteasomal degradation. Interacts with host TP73; this interaction inhibits TP73-mediated apoptotic pathway. Associated with the nuclear matrix. Belongs to the herpesviridae EBNA-6 family.