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The Epstein‐Barr virus bZIP transcription factor Zta causes G0/G1 cell cycle arrest through induction of cyclin‐dependent kinase inhibitors.
Author(s) -
Cayrol C.,
Flemington E. K.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb00635.x
Subject(s) - biology , lytic cycle , cell cycle , virology , cancer , cancer research , virus , genetics
While oncoproteins encoded by small DNA tumor viruses and Epstein‐Barr virus (EBV) latent antigens facilitate G1/S progression, the EBV lytic switch transactivator Zta was found to inhibit growth by causing cell cycle arrest in G0/G1 in several epithelial tumor cell lines. Expression of Zta results in induction of the tumor suppressor protein, p53, and the cyclin‐dependent kinase inhibitors, p21 and p27, as well as accumulation of hypophosphorylated pRb. Up‐regulation of p53 and p27 occurs by post‐transcriptional mechanisms while expression of p21 is induced at the RNA level in a p53‐dependent manner. Inactivation of pRb by transient overexpression of the human papillomavirus E7 oncoprotein indicates that pRb or pRb‐related proteins are key mediators of the growth‐inhibitory function of Zta. These findings suggest that EBV plays an active role in redirecting epithelial cell physiology to facilitate the viral replicative program through a Zta‐mediated growth arrest function.