Abstract
Two potent heat-stable protein phosphatase 2A (PP2A) inhibitor proteins designated I1PP2A and I2PP2A have been purified to apparent homogeneity from extracts of bovine kidney (Li, M., Guo, H., and Damuni, Z. (1995) Biochemistry 34, 1988-1996). N-terminal and internal amino acid sequencing indicated that I2PP2A was a truncated form of SET, a largely nuclear protein that is fused to nucleoporin Nup214 in acute non-lymphocytic myeloid leukemia. Experiments using purified preparations of recombinant human SET confirmed that this protein inhibited PP2A. Half-maximal inhibition of the phosphatase occurred at about 2 nM SET. By contrast, SET (up to 20 nM) did not affect the activities of purified preparations of protein phosphatases 1, 2B, and 2C. The results indicate that SET is a potent and specific inhibitor of PP2A and suggest that impaired regulation of PP2A may contribute to acute myeloid leukemogenesis.
Highlights
A number of defined chromosomal translocations occur in specific subtypes of myeloid leukemia indicating that these translocations play an important role in the process of leukemogenesis [1, 2]
We show that the purified bovine kidney preparations of I2PP2A represent a truncated form of SET [22], a largely nuclear protein termed PHAP-II [23] and TAF [24]
The results suggest that fusion of SET with Nup214 in acute myeloid leukemia may impair the normal regulation of phosphatase 2A (PP2A) and contribute to leukemogenesis
Summary
A number of defined chromosomal translocations occur in specific subtypes of myeloid leukemia indicating that these translocations play an important role in the process of leukemogenesis [1, 2]. We recently purified to apparent homogeneity from extracts of bovine kidney two heat-stable and PP2A-specific inhibitor proteins designated I1PP2A and I2PP2A [21].
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