Vitamin K2 binds 17beta-hydroxysteroid dehydrogenase 4 and modulates estrogen metabolism.
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.
Otsuka
Motoyuki
M
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
Kato
Naoya
N
Ichimura
Tohru
T
Abe
Shinya
S
Tanaka
Yasuo
Y
Taniguchi
Hiroyoshi
H
Hoshida
Yujin
Y
Moriyama
Masaru
M
Wang
Yue
Y
Shao
Run-Xuan
RX
Narayan
Dharel
D
Muroyama
Ryosuke
R
Kanai
Fumihiko
F
Kawabe
Takao
T
Isobe
Toshiaki
T
Omata
Masao
M
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
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