Model of the discordant effects of ZEBRA protein on p53-dependent transcription in different cell types.

In B lymphocytes in which ZEBRA is demonstrated to localize to the cell nucleus, binding between p53 and ZEBRA in the nucleus reduces transcriptional activity of both proteins through a direct protein–protein interaction. In T lymphocytes, interactions between ZEBRA and components of the cell cytoplasm or cytoskeleton (“cell stress”) activate cytoplasmic p53 activating kinases, such as ATM, independently of direct binding between ZEBRA and p53. “Cell stress” mediated by cytoplasmic ZEBRA may also contribute to the abnormal morphology of Jurkat cells stably expressing ZEBRA protein. An important prediction of this model is that relocation of ZEBRA to the cytoplasm by either post-translational modification or other mechanisms may reverse the effects of ZEBRA on p53-dependent transcription and cellular apoptosis in EBV-infected cells.