Epigenetically mediated loss of UDP-GlcNAc 2-epimerase/ManNAc kinase expression in hyposialylated cell lines.
The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase is the key enzyme in sialic acid biosynthesis. Loss of UDP-GlcNAc 2-epimerase activity results in a hyposialylated phenotype as shown for two human hematopoietic cell lines that lack the specific mRNA. We found that treatment with the DNA methylation inhibitor 5'-aza-2'-deoxycytidine (5-aza-dC) restored the UDP-GlcNAc 2-epimerase/ManNAc kinase mRNA, as well as enzyme activity and cell surface sialylation. Increase of UDP-GlcNAc 2-epimerase activity by 5-aza-dC treatment was also found for a rat Morris hepatoma cell line. These results indicate a regulation of UDP-GlcNAc 2-epimerase/ManNAc kinase expression on the transcriptional level by DNA methylation.
Oetke
Cornelia
C
Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Hinderlich
Stephan
S
Reutter
Werner
W
Pawlita
Michael
M
D000818:Animals; D002238:Carbohydrate Epimerases / Q000378:metabolism* / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008745:Methylation; D019158:N-Acetylneuraminic Acid / Q000096:biosynthesis / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D012333:RNA, Messenger; D004247:DNA; D008156:Luciferases; D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase; D019158:N-Acetylneuraminic Acid