Vitamin K2 binds 17beta-hydroxysteroid dehydrogenase 4 and modulates estrogen metabolism

Life Sci. 2005 Apr 8;76(21):2473-82. doi: 10.1016/j.lfs.2004.12.020.

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.

Publication types

  • Comparative Study

MeSH terms

  • 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

Substances

  • Apolipoproteins E
  • Biomarkers
  • Estrogens
  • Multienzyme Complexes
  • Protein Precursors
  • RPS13 protein, human
  • Ribosomal Proteins
  • ribosomal protein S7
  • Vitamin K 2
  • Estrone
  • Estradiol
  • acarboxyprothrombin
  • Prothrombin
  • 17-Hydroxysteroid Dehydrogenases
  • Hydro-Lyases
  • Peroxisomal Multifunctional Protein-2
  • HSD17B4 protein, human
  • Enoyl-CoA Hydratase