Antagonistic regulation of cell-matrix adhesion by FosB and DeltaFosB/Delta2DeltaFosB encoded by alternatively spliced forms of fosB transcripts

Mol Biol Cell. 2008 Nov;19(11):4717-29. doi: 10.1091/mbc.e07-08-0768. Epub 2008 Aug 27.


Among fos family genes encoding components of activator protein-1 complex, only the fosB gene produces two forms of mature transcripts, namely fosB and DeltafosB mRNAs, by alternative splicing of an exonic intron. The former encodes full-length FosB. The latter encodes DeltaFosB and Delta2DeltaFosB by alternative translation initiation, and both of these lack the C-terminal transactivation domain of FosB. We established two mutant mouse embryonic stem (ES) cell lines carrying homozygous fosB-null alleles and fosB(d) alleles, the latter exclusively encoding DeltaFosB/Delta2DeltaFosB. Comparison of their gene expression profiles with that of the wild type revealed that more than 200 genes were up-regulated, whereas 19 genes were down-regulated in a DeltaFosB/Delta2DeltaFosB-dependent manner. We furthermore found that mRNAs for basement membrane proteins were significantly up-regulated in fosB(d/d) but not fosB-null mutant cells, whereas genes involved in the TGF-beta1 signaling pathway were up-regulated in both mutants. Cell-matrix adhesion was remarkably augmented in fosB(d/d) ES cells and to some extent in fosB-null cells. By analyzing ES cell lines carrying homozygous fosB(FN) alleles, which exclusively encode FosB, we confirmed that FosB negatively regulates cell-matrix adhesion and the TGF-beta1 signaling pathway. We thus concluded that FosB and DeltaFosB/Delta2DeltaFosB use this pathway to antagonistically regulate cell matrix adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Alternative Splicing / genetics*
  • Animals
  • Basement Membrane / metabolism
  • Cell Adhesion
  • Cell Line
  • Cell-Matrix Junctions / metabolism*
  • Embryonic Stem Cells / metabolism
  • Gene Expression Profiling
  • Gene Targeting
  • Mice
  • Models, Biological
  • Mutant Proteins / metabolism*
  • Mutation / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins c-fos / deficiency
  • Proto-Oncogene Proteins c-fos / genetics*
  • Proto-Oncogene Proteins c-fos / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation


  • Mutant Proteins
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Transforming Growth Factor beta