The EBNA- 3 gene family proteins disrupt the G2/M checkpoint

Krauer, Kenia G., Burgess, Andrew, Buck, Marion, Flanagan, James, Sculley, Tom B. and Gabrielli, Brian (2004) The EBNA- 3 gene family proteins disrupt the G2/M checkpoint. Oncogene, 23 7: 1342-1353. doi:10.1038/sj.onc.1207253


Author Krauer, Kenia G.
Burgess, Andrew
Buck, Marion
Flanagan, James
Sculley, Tom B.
Gabrielli, Brian
Title The EBNA- 3 gene family proteins disrupt the G2/M checkpoint
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
1476-5594
Publication date 2004
Sub-type Article (original research)
DOI 10.1038/sj.onc.1207253
Volume 23
Issue 7
Start page 1342
End page 1353
Total pages 12
Place of publication London, United Kingdom
Publisher Nature
Collection year 2004
Language eng
Abstract 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.
Keyword Chk2
EBNA-3
EBV
G2/M checkpoint
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 03:06:17 EST