Komori A, Sueoka E, Fujiki H, Ishii M, Kozu T
Saitama Cancer Center Research Institute.
Jpn J Cancer Res. 1999 Jan;90(1):60-8. doi: 10.1111/j.1349-7006.1999.tb00666.x.
A proto-oncogene, MTG8 (ETO/CDR), is disrupted in the t(8;21) translocation associated with acute myeloid leukemia, and the gene product, MTG8, is a phosphoprotein capable of cell transformation in concert with v-H-ras. To obtain insight into functional regulation of MTG8 by phosphorylation, we studied protein kinases that interact with, and phosphorylate, MTG8 in vitro. Recombinant MTG8 protein was first found to be associated with two serine/threonine protein kinases in cell extracts from both HEL cells and a leukemic cell line carrying t(8;21). A cytoplasmic protein kinase of 61 kDa (MTG8N-kinase) phosphorylated the amino-terminal of MTG8, and another of 52 kDa (MTG8C-kinase) phosphorylated the carboxyl-terminal domain. In addition, we demonstrated that heat shock protein 90 (HSP90) specifically binds to the amino-terminal domain of MTG8 in vitro and in vivo. Thus, our results shed new light on post-translational regulation of MTG8, perturbation of which, in AML1-MTG8 protein, probably contributes to leukemogenesis.
一种原癌基因MTG8（ETO/CDR）在与急性髓性白血病相关的t(8;21)易位中被破坏，其基因产物MTG8是一种磷蛋白，能够与v-H-ras协同进行细胞转化。为了深入了解MTG8磷酸化的功能调控，我们研究了在体外与MTG8相互作用并使其磷酸化的蛋白激酶。首先发现重组MTG8蛋白与HEL细胞和携带t(8;21)的白血病细胞系的细胞提取物中的两种丝氨酸/苏氨酸蛋白激酶相关。一种61 kDa的细胞质蛋白激酶（MTG8N激酶）使MTG8的氨基末端磷酸化，另一种52 kDa的蛋白激酶（MTG8C激酶）使羧基末端结构域磷酸化。此外，我们证明热休克蛋白90（HSP90）在体外和体内均特异性结合MTG8的氨基末端结构域。因此，我们的结果为MTG8的翻译后调控提供了新的线索，在AML1-MTG8蛋白中这种调控的扰动可能促成白血病的发生。
