O-Linked GlcNAc transferase is a conserved nucleocytoplasmic protein containing tetratricopeptide repeats.
O-Linked GlcNAc addition and phosphorylation may compete for sites on nuclear pore proteins and transcription factors. We sequenced O-linked GlcNAc transferase from rabbit blood and identified the homologous Caenorhabditis elegans transferase gene on chromosome III. We then isolated C. elegans and human cDNAs encoding the transferase. The enzymes from the two species appear to be highly conserved; both contain multiple tetratricopeptide repeats and nuclear localization sequences. The C. elegans transferase accumulated in the nucleus and in perinuclear aggregates in overexpressing transgenic lines. O-Linked GlcNAc transferase activity was also elevated in HeLa cells transfected with the human cDNA. At least four human transcripts were observed in the tissues examined ranging in size from 4.4 to 9.3 kilobase pairs. The two largest transcripts (7.9 and 9.3 kilobase pairs) were enriched at least 12-fold in the pancreas. Based on its substrate specificity and molecular features, we propose that O-linked GlcNAc transferase is part of a glucose-responsive pathway previously implicated in the pathogenesis of diabetes mellitus.
Lubas
W A
WA
Laboratory of Cell Biochemistry and Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
Frank
D W
DW
Krause
M
M
Hanover
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000737:chemistry; D019143:Evolution, Molecular; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry* / Q000235:genetics; D011817:Rabbits; D012091:Repetitive Sequences, Nucleic Acid
D018076:DNA, Complementary; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase