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The immunosuppressive drug mizoribine has been demonstrated to inhibit T lymphocyte proliferation by depleting these cells of guanine ribonucleotides as a consequence of inhibiting the enzyme inosine monophosphate (IMP) dehydrogenase. Because the immunosuppressive agents azathioprine and 6-mercaptopurine (6MP) are both converted to the IMP analog(More)
Inosine monophosphate dehydrogenase (IMPDH) catalyzes the first step in the formation of guanine ribonucleotides from inosine monophosphate and the activity of this enzyme appears to be essential for cell proliferation. Inhibitors of IMPDH have been demonstrated to be effective immunosuppressive agents and to inhibit T cell activation in vitro. IMPDH(More)
The immunosuppressive drug, mizoribine, has been used to prevent rejection of organ allografts in humans and in animal models. Based on studies in cell lines, mizoribine has been postulated to be an inhibitor of inosine monophosphate (IMP) dehydrogenase (EC1.2.1.14), a pivotal enzyme in the formation of guanine ribonucleotides from IMP. To further(More)
Inhibitors of IMP dehydrogenase (EC 1.2.1.14), including mizoribine (Bredinin) and mycophenolic acid, have significant antitumor and immunosuppressive activities. Studies were aimed at determining the mechanism by which intracellular GTP depletion induced by these agents results in inhibition of DNA synthesis. Incubation of human CEM leukemia cells for 2 hr(More)
IMP dehydrogenase is a key enzyme in the de novo pathway of purine biosynthesis and is responsible for catalyzing the first step in the formation of guanine ribonucleotides from inosine monophosphate. Mizoribine, an immunosuppressive agent in wide-spread clinical use in Japan, has been demonstrated to inhibit this enzyme. We have investigated the effects of(More)
The goal of this review is to summarise the current knowledge concerning the targets of Ca++/calmodulin that are essential for cell cycle progression in lower eukaryotes. Emphasis is placed on Aspergillus nidulans since this is the only organism to date shown to posses essential Ca++ dependent calmodulin activated enzymes. Two such enzymes are the(More)
The unique gene for Ca2+/calmodulin-dependent protein kinase (CaMK) has been shown to be essential in Aspergillus nidulans. Disruption of the gene prevents entry of spores into the nuclear division cycle. Here we show that expression of a constitutively active form of CaMK also prevents spores from entering the first S phase in response to a germinating(More)
The calmodulin gene has been shown to be essential for cell cycle progression in a number of eukaryotic organisms. In vertebrates and Aspergillus nidulans the calmodulin dependence also requires calcium. We demonstrate that the unique gene encoding a multifunctional calcium/calmodulin-dependent protein kinase (CaMK) is also essential in A. nidulans. This(More)
The human deoxycytidine kinase gene is a single copy gene and is comprised of seven exons that are spread over more than 34 kb of the genome. The 5'-flanking region is highly G/C rich and does not contain CAAT or TATA boxes. This region, when cloned into a recorder gene construct containing the chloramphenicol acetyltransferase gene, is capable of mediating(More)