Nagai M, Natsumeda Y, Weber G
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46202-5200.
Cancer Res. 1992 Jan 15;52(2):258-61.
Human IMP dehydrogenase (IMPDH; EC 1.1.1.205) was recently found to consist of two molecular species (types I and II) with high expression of type II isozyme in leukemic cells. Here we report that the low level of type II mRNA in normal lymphocytes was up-regulated by phytohemagglutinin stimulation (3.2-fold) and Epstein-Barr viral transformation (5.7-fold). The type II mRNA expression in quiescent HL-60 cells was also elevated 2.8-fold by serum stimulation. Conversely the enhanced level of type II IMPDH mRNA in HL-60 cells was down-regulated to less than 5% along with differentiation induced by retinoic acid (1 microM), phorbol-12-myristate-13-acetate (33 nM), or dimethyl sulfoxide (1.25%) independent of end-stage phenotype. By contrast, type I IMPDH mRNA was expressed constitutively in the various states of proliferation and differentiation. The type II IMPDH stringently linked with cell proliferation should be a crucial target for antileukemic and immunosuppressive chemotherapy.
人肌苷酸脱氢酶（IMPDH；EC 1.1.1.205）最近被发现由两种分子形式（I型和II型）组成，其中II型同工酶在白血病细胞中高表达。在此我们报告，正常淋巴细胞中II型mRNA的低水平在植物血凝素刺激（3.2倍）和爱泼斯坦-巴尔病毒转化（5.7倍）后上调。静止的HL-60细胞中II型mRNA的表达在血清刺激后也升高了2.8倍。相反，HL-60细胞中II型IMPDH mRNA的增强水平在视黄酸（1 microM）、佛波醇-12-肉豆蔻酸酯-13-乙酸酯（33 nM）或二甲基亚砜（1.25%）诱导分化后下调至5%以下，且与终末表型无关。相比之下，I型IMPDH mRNA在增殖和分化的各种状态下均组成性表达。与细胞增殖紧密相关的II型IMPDH应是抗白血病和免疫抑制化疗的关键靶点。
