Division of Tumor Virology, Division of Neoplastic Disease Mechanisms, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
EMBO J 15: 2748-59 (1996)
Abstract
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.
Mesh Headings
Unique Identifier: 96256292
Chemical Identifiers (Names)