PP2A targeting by viral proteins: A widespread biological strategy from DNA/RNA tumor viruses to HIV-1

Protein phosphatase 2A (PP2A) is a large family of holoenzymes that comprises 1% of total cellular proteins and accounts for the majority of Ser/Thr phosphatase activity in eukaryotic cells. Although initially viewed as constitutive housekeeping enzymes, it is now well established that PP2A proteins represent a family of highly and sophistically regulated phosphatases. The past decade, multiple complementary studies have improved our knowledge about structural and functional regulation of PP2A holoenzymes. In this regard, after summarizing major cellular regulation, this review will mainly focus on discussing a particulate biological strategy, used by various viruses, which is based on the targeting of PP2A enzymes by viral proteins in order to specifically deregulate, for their own benefit, cellular pathways of their hosts. The impact of such PP2A targeting for research in human diseases, and in further therapeutic developments, is also discussed.

► The family of PP2A holoenzymes are specific targets for multiple viruses.
► Viruses use PP2A to specifically subvert key survival pathways of their hosts.
► Proteins encoded by DNA/RNA tumor viruses bind PP2A to activate oncogenic pathways.
► PP2A dysfunction is associated to cancer and neurodegeneration.
► The study of PP2A dysfunction is a powerful approach for human therapy.