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The adenovirus E4orf4 protein targets PP2A to the ACF chromatin remodeling factor and controls cell death through different SNF2h‐containing complexes
Author(s) -
Kleinberger Tamar,
Brestovitsky Anna,
Sharf Rakefet
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.892.1
Subject(s) - chromatin structure remodeling (rsc) complex , chromatin remodeling , protein phosphatase 2 , chromatin , biology , gene knockdown , microbiology and biotechnology , programmed cell death , adenovirus infection , apoptosis , protein subunit , gene , genetics , virus
The adenovirus E4orf4 protein regulates the progression of viral infection and when expressed individually it induces non‐classical apoptosis in transformed cells. Here we show that E4orf4 associates with the ATP‐dependent chromatin remodeling factor ACF that consists of a SNF2h ATPase and an Acf1 regulatory subunit. Furthermore, E4orf4 targets protein phosphatase 2A (PP2A) to this complex and to chromatin. Obstruction of SNF2h activity inhibits E4orf4‐induced cell death, whereas knockdown of Acf1 results in enhanced E4orf4‐induced toxicity in both mammalian and yeast cells, and Acf1 overexpression inhibits E4orf4's ability to downregulate early adenovirus gene expression in the context of viral infection. Knockdown of the Acf1 homologue, WSTF, inhibits E4orf4‐induced cell death. Based on these results we suggest that the E4orf4‐PP2A complex inhibits ACF and facilitates enhanced chromatin remodeling activities of other SNF2h‐containing complexes, such as WSTF‐SNF2h. The resulting switch in chromatin remodeling determines life vs. death decisions and contributes to E4orf4 functions during adenovirus infection.