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Protein phosphatase 2A (PP2A) is a major mammalian protein serine/threonine phosphatase that regulates diverse cellular processes. Inhibitor 1 of PP2A (I1PP2A) and inhibitor 2 of PP2A (I2PP2A), which share large sequence similarity, are heat-stable protein inhibitors of the cellular phosphatase activity of PP2A. I1PP2A and I2PP2A were initially characterized as putative HLA class II associated proteins Phap I and Phap II. These inhibitor proteins act noncompetitively to selectively inhibit PP2A, but do not affect the phosphatase activity of the related proteins PP1, PP2B and PP2C. The I1PP2A protein is localized to both the cytoplasm and the nucleus. In contrast, I2PP2A is located predominantly in the nucleus and is highly expressed in Wilms tumor cells. Transient expression of I2PP2A in HEK-293 cells leads to an increase in the DNA binding activity of the proto-oncogene c-Jun.
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