Estradiol-regulated transamidation of keratins by vaginal epithelial cell transglutaminase

Exp Cell Res. 1994 Sep;214(1):358-66. doi: 10.1006/excr.1994.1268.


We have observed a marked increase in the activity of transglutaminase (EC in rat vaginal epithelial cells in a time-dependent manner during estradiol-induced terminal differentiation. The increased transglutaminase activity facilitates a post-translational modification, transamidation of keratins by the formation of an isopeptide sigma (tau-glutamyl) lysine. This isopeptide was recovered from the urea-soluble and -insoluble fractions of keratins. The formation of sigma (tau-glutamyl) lysine was significantly reduced in rats primed with progesterone or tamoxifen-estradiol. These in vivo experiments were further confirmed by in vitro studies using the reconstituted keratin filaments, which demonstrated a remarkable acceleration in the formation of covalent cross-links mediated by vaginal epithelial cell transglutaminase obtained from rats primed with estradiol. By specifically modifying the lysine residues of the keratins with 2,4-pentanedione the aggregation of keratin filaments was inhibited. These findings reflect that the vaginal epithelial cell transglutaminase obtained from rats which is regulated by estradiol plays a key role in the process of terminal differentiation of rat vaginal epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / metabolism
  • Animals
  • Calcium / metabolism
  • Epithelium / drug effects
  • Epithelium / enzymology
  • Epithelium / metabolism
  • Estradiol / pharmacology*
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Glutamates / metabolism
  • Glutamic Acid
  • Hydrolysis
  • Keratins / metabolism*
  • Lysine / metabolism
  • Protein Conformation
  • Protein Processing, Post-Translational
  • Rats
  • Rats, Wistar
  • Solubility
  • Transglutaminases / metabolism*
  • Vagina / drug effects
  • Vagina / enzymology
  • Vagina / metabolism*


  • Amides
  • Glutamates
  • Glutamic Acid
  • Estradiol
  • Keratins
  • Transglutaminases
  • Lysine
  • Calcium