The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A.
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.
Li
M
M
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey 17033, USA.
Makkinje
A
A
Damuni
Z
Z
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D056488:Histone Chaperones; D006801:Humans; D007668:Kidney / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010449:Peptide Mapping; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D014176:Protein Biosynthesis; D054648:Protein Phosphatase 2; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000494:pharmacology; D014157:Transcription Factors; D014357:Trypsin
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D056488:Histone Chaperones; D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins; C513473:SET protein, human; D014157:Transcription Factors; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D014357:Trypsin