Adenovirus E4orf4 protein induces PP2A-dependent growth arrest in Saccharomyces cerevisiae and interacts with the anaphase-promoting complex/cyclosome

Citation
D. Kornitzer et al., Adenovirus E4orf4 protein induces PP2A-dependent growth arrest in Saccharomyces cerevisiae and interacts with the anaphase-promoting complex/cyclosome, J CELL BIOL, 154(2), 2001, pp. 331-344
Citations number
82
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
154
Issue
2
Year of publication
2001
Pages
331 - 344
Database
ISI
SICI code
0021-9525(20010723)154:2<331:AEPIPG>2.0.ZU;2-G
Abstract
A denovirus early region 4 open reading frame 4 (E4orf4) protein has been r eported to induce p133-independent, protein phosphatase 2A (PP2A)-dependent apoptosis in transformed mammalian cells. In this report, we show that E4o rf4 induces an irreversible growth arrest in Saccharomyces cerevisiae at th e G(2)/M phase of the cell cycle. Growth inhibition requires the presence o f yeast PP2A-Cdc55, and is accompanied by accumulation of reactive oxygen s pecies. E4orf4 expression is synthetically lethal with mutants defective in mitosis, including Cdc28/Cdk1 and anaphase-promoting complex/cyclosome (AP C/C) mutants. Although APC/C activity is inhibited in the presence of E4orf 4, Cdc28/Cdk1 is activated and partially counteracts the E4orf4-induced cel l cycle arrest. The E4orf4-PP2A complex physically interacts with the APC/C , suggesting that E4orf4 functions by directly targeting PP2A to the APC/C, thereby leading to its inactivation. Finally, we show that E4orf4 can indu ce G(2)/M arrest in mammalian cells before apoptosis, indicating that E4orf 4-induced events in yeast and mammalian cells are highly conserved.