14-3-3 protein family members have a regulatory role in retinoic acid-mediated induction of cytokeratins in F9 cells

Exp Cell Res. 2000 Oct 10;260(1):96-104. doi: 10.1006/excr.2000.4991.


We have found that the expression of five 14-3-3 protein isoforms is induced during the retinoic acid (RA)-mediated differentiation of mouse embryonal carcinoma F9 cells. The induced expression of the 14-3-3 proteins is presumed to have a role in enhancing the mitogen-activated protein kinase (MAPK) activity during RA-mediated F9 cell differentiation, because using genetically engineered budding yeast we showed that these isoforms enhanced the signaling in the MAPK cascade mainly through the interaction with Raf-1. Then we assessed the role of increased MAPK activity in F9 cell differentiation by interfering with signaling in the MAPK cascade in F9 cells. The exogenous expression of dominant-negative MEK1 efficiently abrogated RA-mediated induction of the cytokeratins EndoA and EndoC in the F9 cells. These results suggest that the 14-3-3 proteins play a role in the efficient induction of the cytokeratins during F9 cell differentiation through their signal enhancing activity in the MAPK cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins
  • Animals
  • Cell Differentiation / drug effects
  • Cycloheximide / pharmacology
  • DNA, Complementary / genetics
  • Gene Expression / drug effects
  • Keratins / biosynthesis*
  • MAP Kinase Signaling System
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Synthesis Inhibitors / pharmacology
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism*


  • 14-3-3 Proteins
  • DNA, Complementary
  • Protein Isoforms
  • Protein Synthesis Inhibitors
  • Tretinoin
  • Keratins
  • Cycloheximide
  • Tyrosine 3-Monooxygenase
  • Mitogen-Activated Protein Kinases