The EBNA-3 gene family proteins disrupt the G2/M checkpoint.
The Epstein-Barr nuclear antigens (EBNA), EBNA-3, -4 and -6, have previously been shown to act as transcriptional regulators, however, this study identifies another function for these proteins, disruption of the G2/M checkpoint. Lymphoblastoid cell lines (LCLs) treated with a G2/M initiating drug azelaic bishydroxamine (ABHA) did not show a G2/M checkpoint response, but rather they display an increase in cell death, a characteristic of sensitivity to the cytotoxic effects of the drug. Cell cycle analysis demonstrated that the individual expression of EBNA-3, -4 or -6 are capable of disrupting the G2/M checkpoint response induced by ABHA resulting in increased toxicity, whereas EBNA-2, and -5 were not. EBNA-3 gene family protein expression also disrupted the G2/M checkpoint initiated in response to the genotoxin etoposide and the S phase inhibitor hydroxyurea. The G2 arrest in response to these drugs were sensitive to caffeine, suggesting that ATM/ATR signalling in these checkpoint responses may be blocked by the EBNA-3 family proteins. The function of EBNA-3, -4 and -6 proteins appears to be more complex than anticipated and these data suggest a role for these proteins in disrupting the host cell cycle machinery.
Pubmed ID: 14716295 RIS Download
Ataxia Telangiectasia Mutated Proteins | Cell Cycle Proteins | Checkpoint Kinase 2 | DNA Damage | DNA-Binding Proteins | Epstein-Barr Virus Nuclear Antigens | G2 Phase | Histone Deacetylase Inhibitors | Humans | Hydroxamic Acids | Mitosis | Precipitin Tests | Protein-Serine-Threonine Kinases | Signal Transduction | Tumor Suppressor Proteins