Two distinct cDNAs for human IMP dehydrogenase.
IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP biosynthesis, is a promising target in antileukemic chemotherapy. We have isolated two distinct cDNA clones (types I and II) encoding IMP dehydrogenase from a human spleen cDNA library. Both clones encode closely related proteins of 514 residues showing 84% sequence identity. Northern hybridization analyses of poly(A)+ RNA from human normal leukocytes and human ovarian tumors demonstrated a striking contrast in mRNA expression in that type I mRNA is the main species in normal leukocytes and type II predominates over type I in the tumor. This is the first report suggesting the existence of two distinct types of human IMP dehydrogenase molecular species which may have different sensitivities to the drugs targeted against IMP dehydrogenase.
Natsumeda
Y
Y
Department of Molecular Biology, Tokyo Metropolitan Institute of Medical Science, Japan.
Ohno
S
S
Kawasaki
H
H
Konno
Y
Y
Weber
G
G
Suzuki
K
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics*; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics*; D007658:Ketone Oxidoreductases / Q000235:genetics*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000201:enzymology
D007527:Isoenzymes; D015345:Oligonucleotide Probes; D004247:DNA; D007168:IMP Dehydrogenase; D007658:Ketone Oxidoreductases