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Adenovirus E4orf4 protein interacts with both Bα and B′ subunits of protein phosphatase 2A, but E4orf4-induced apoptosis is mediated only by the interaction with Bα

Oncogene volume 19, pages 3757–3765 (2000)Cite this article

Abstract

Adenovirus E4orf4 protein is a multifunctional viral regulator, which is involved in down regulation of virally-modulated signal transduction, in control of alternative splicing of viral mRNAs, and in induction of apoptosis in transformed cells. It has been previously shown that E4orf4 interacts with protein phosphatase 2A through the phosphatase Bα subunit. It was further shown that PP2A is required for performing the various E4orf4 functions. We report here that E4orf4 interacts with multiple isoforms of the PP2A-B′ subunit, as well as with Bα. We map the interaction sites of the B subunits on E4orf4 and show that they overlap but are not identical. We identify a dominant negative E4orf4 mutant, which disrupts the PP2A holoenzyme. We show that induction of apoptosis by E4orf4, which we previously reported to require the interaction with Bα, is not affected by the interaction with B′. Our results suggest that the interaction of E4orf4 with various PP2A subpopulations may mediate the different E4orf4 functions.

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Acknowledgements

We thank D M Virshup for the plasmids encoding HA-tagged B′ subunits and D Frank for his comments on the manuscript. This work was supported by grants from the Israel Science Foundation founded by the Israel Academy of Sciences and Humanities, the Israel Cancer Association, and the Fund for the Promotion of Research at the Technion.

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  1. The Gonda Center of Molecular Microbiology, The B. Rappaport Faculty of Medicine, Technion, 31096, Haifa, Israel

    Ronit Shtrichman, Rakefet Sharf & Tamar Kleinberger

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  1. Ronit Shtrichman
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Shtrichman, R., Sharf, R. & Kleinberger, T. Adenovirus E4orf4 protein interacts with both Bα and B′ subunits of protein phosphatase 2A, but E4orf4-induced apoptosis is mediated only by the interaction with Bα. Oncogene 19, 3757–3765 (2000). https://doi.org/10.1038/sj.onc.1203705

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