Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase. This enzyme is involved in a plethora of cellular processes, including apoptosis, autophagy, cell proliferation, and DNA repair. Remarkably, PP2A can act as a context-dependent tumor suppressor or promoter. Active PP2A complexes consist of structural (PP2A-A), regulatory (PP2A-B), and catalytic (PP2A-C) subunits. The regulatory subunits define the substrate specificity and the subcellular localization of the holoenzyme. Here we condense the increasing evidence that the PP2A B-type subunit PR130 is a critical regulator of cell identity and oncogenic transformation. We summarize knowledge on the biological functions of PR130 in normal and transformed cells, targets of the PP2A-PR130 complex, and how diverse extra- and intracellular stimuli control the expression and activity of PR130. We additionally review the impact of PP2A-PR130 on cardiac functions, neuronal processes, and anti-viral defense and how this might affect cancer development and therapy.
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