Proliferation-linked regulation of type II IMP dehydrogenase gene in human normal lymphocytes and HL-60 leukemic cells.
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.
Nagai
M
M
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46202-5200.
Natsumeda
Y
Y
Weber
G
G
D015152:Blotting, Northern; D002455:Cell Division; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006151:Guanosine / Q000494:pharmacology; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D007951:Leukemia, Myeloid / Q000201:enzymology* / Q000473:pathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D012254:Ribavirin / Q000031:analogs & derivatives / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D006151:Guanosine; D012254:Ribavirin; D014212:Tretinoin; D007168:IMP Dehydrogenase; D013755:Tetradecanoylphorbol Acetate; C033706:tiazofurin; D004121:Dimethyl Sulfoxide