RRC ID 42327
Author Otsuka M, Kato N, Ichimura T, Abe S, Tanaka Y, Taniguchi H, Hoshida Y, Moriyama M, Wang Y, Shao RX, Narayan D, Muroyama R, Kanai F, Kawabe T, Isobe T, Omata M.
Title Vitamin K2 binds 17beta-hydroxysteroid dehydrogenase 4 and modulates estrogen metabolism.
Journal Life Sci.
Abstract Vitamin K is a cofactor for gamma-glutamyl carboxylase, an enzyme that is important for blood coagulation. Recent studies have shown that vitamin K has other roles, in addition to post-transcriptional modification, such as bone metabolism and antitumoral actions; these findings have indicated that there might be unknown intracellular binding proteins that are specific for vitamin K. In this study, vitamin K-binding proteins were characterized by pull-down experiment using a chemically synthesized biotynylated vitamin K followed by mass spectrometric identification of the pull-downed components. The results indicated that 17beta hydroxy steroid dehydrogenase 4, apolipoportein E, and 40S ribosomal proteins S7 and S13 might be the candidates of the vitamin K-binding proteins. Subsequent experiments showed that vitamin K2 binds 17beta hydroxysteroid dehydrogenase 4 and decreases the intracellular estradiol:estrone ratio, which resulted in the inhibition of the amount of estrogen receptor alpha-binding to its target DNA. These results suggest a possible novel role for vitamin K in modulating estrogen function.
Volume 76(21)
Pages 2473-82
Published 2005-4-8
DOI 10.1016/j.lfs.2004.12.020
PII S0024-3205(05)00043-3
PMID 15763078
MeSH 17-Hydroxysteroid Dehydrogenases / genetics 17-Hydroxysteroid Dehydrogenases / metabolism* Amino Acid Sequence Apolipoproteins E / metabolism Biomarkers / metabolism Blotting, Western Chromatography, Liquid Electrophoresis, Polyacrylamide Gel Enoyl-CoA Hydratase / genetics Enoyl-CoA Hydratase / metabolism* Enzyme-Linked Immunosorbent Assay Estradiol / metabolism Estrogens / metabolism* Estrone / metabolism Humans Hydro-Lyases Mass Spectrometry Molecular Sequence Data Multienzyme Complexes / genetics Multienzyme Complexes / metabolism* Peroxisomal Multifunctional Protein-2 Plasmids / genetics Protein Binding Protein Precursors / metabolism Prothrombin / metabolism Ribosomal Proteins / metabolism Sequence Analysis, Protein Transcriptional Activation / drug effects Transfection Tumor Cells, Cultured Vitamin K 2 / chemistry Vitamin K 2 / metabolism* Vitamin K 2 / pharmacology
IF 3.234
Times Cited 16
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL PHARMACOLOGY & PHARMACY
Resource
Human and Animal Cells