The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A
The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A
复制标题
DOI：
10.1074/jbc.271.19.11059
复制
发表时间：
1996-05-10
影响因子：
4.8
通讯作者：
Damuni, Z
中科院分区：
文献类型：
--
作者：
Li, M;Makkinje, A;Damuni, Z
两种有效的热稳定蛋白磷酸酶2A（PP 2A）抑制剂蛋白质，命名为I-1（PP 2A）和I-2（PP 2A），已经从牛肾提取物中纯化至表观均一性（Li，M.，郭，H.，和Damuni，Z.（1995）Biochemistry 34，1988-1996）。N-末端和内部氨基酸测序表明，I-2（PP 2A）是SET的截短形式，SET是一种主要的核蛋白，在急性非淋巴细胞性髓性白血病中与核孔蛋白Nup 214融合。使用重组人SET的纯化制备物的实验证实，该蛋白质抑制PP 2A。磷酸酶的半数最大抑制发生在约2 nM SET。相比之下，SET（高达20 nM）不影响蛋白磷酸酶1，2B和2C的纯化制剂的活性。结果表明，SET是一种有效的和特异性的抑制剂的PP 2A，并表明，受损的调节PP 2A可能有助于急性髓性白血病的发生。
Two potent heat-stable protein phosphatase 2A (PP2A) inhibitor proteins designated I-1(PP2A) and I-2(PP2A) 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 I-2(PP2A) 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.