title: Vitamin K2 binds 17beta-hydroxysteroid dehydrogenase 4 and modulates estrogen metabolism.
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.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. motoootsuka-gi@umin.ac.jp
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.forename: Naoya
authors.initials: N
authors.lastname: Kato
authors.forename: Tohru
authors.initials: T
authors.lastname: Ichimura
authors.forename: Shinya
authors.initials: S
authors.lastname: Abe
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Yujin
authors.initials: Y
authors.lastname: Hoshida
authors.forename: Masaru
authors.initials: M
authors.lastname: Moriyama
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Run-Xuan
authors.initials: RX
authors.lastname: Shao
authors.forename: Dharel
authors.initials: D
authors.lastname: Narayan
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Muroyama
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kanai
authors.forename: Takao
authors.initials: T
authors.lastname: Kawabe
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Isobe
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001057:Apolipoproteins E / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D004746:Enoyl-CoA Hydratase / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D004970:Estrone / Q000378:metabolism; D006801:Humans; D006836:Hydro-Lyases; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D064029:Peroxisomal Multifunctional Protein-2; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D020539:Sequence Analysis, Protein; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D024482:Vitamin K 2 / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D004967:Estrogens; D009097:Multienzyme Complexes; D011498:Protein Precursors; C047013:RPS13 protein, human; D012269:Ribosomal Proteins; C037442:ribosomal protein S7; D024482:Vitamin K 2; D004970:Estrone; D004958:Estradiol; C008208:acarboxyprothrombin; D011516:Prothrombin; D015067:17-Hydroxysteroid Dehydrogenases; D006836:Hydro-Lyases; D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human; D004746:Enoyl-CoA Hydratase