Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.12.2 (
MEK
)
18,161
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The importance of heparan- and chondroitin-sulfate proteoglycans in physiological and pathological processes led to the investigation of the regulation of beta1,3-
glucuronosyltransferase I
(
GlcAT-I
), responsible for the completion of glycosaminoglycan-protein linkage tetrasaccharide, a key step prior to polymerization of chondroitin- and heparan-sulfate chains. We have cloned and functionally characterized
GlcAT-I
5'-flanking regulatory region. Mutation analysis and electrophoretic mobility shift assays demonstrated the importance of Sp1 motif located at -65/-56 position in promoter activity. Furthermore, we found that elevation of intracellular calcium concentration by the calcium ionophore ionomycin stimulated
GlcAT-I
gene expression as well as glycosaminoglycan chain synthesis in HeLa cells. Bisanthracycline, an anti-Sp1 compound, inhibited
GlcAT-I
basal promoter activity and suppressed ionomycin induction, suggesting the importance of Sp1 in calcium induction of
GlcAT-I
gene expression. Nuclear protein extracts from ionomycin-induced cells exhibited an increased DNA binding of Sp1 factor to the consensus sequence at position -65/-56. Signaling pathway analysis and
MEK
inhibition studies revealed the important role of p42/p44 MAPK in the stimulation of
GlcAT-I
promoter activity by ionomycin. The present study identifies, for the first time,
GlcAT-I
as a target of calcium-dependent signaling pathway and evidences the critical role of Sp1 transcription factor in the activation of
GlcAT-I
expression.
...
PMID:Evidence of calcium-dependent pathway in the regulation of human beta1,3-glucuronosyltransferase-1 (GlcAT-I) gene expression: a key enzyme in proteoglycan synthesis. 1680 73
