Antagonistic regulation of cell-matrix adhesion by FosB and ΔFosB/Δ2ΔFosB encoded by alternatively spliced forms of fosB transcripts

Yoshinori N. Ohnishi, Kunihiko Sakumi, Katsuhisa Yamazaki, Yoko H. Ohnishi, Tomofumi Miura, Yohei Tominaga, Yusaku Nakabeppu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Among fos family genes encoding components of activator protein-1 complex, only the fosB gene produces two forms of mature transcripts, namely fosB and ΔfosB mRNAs, by alternative splicing of an exonic intron. The former encodes full-length FosB. The latter encodes ΔFosB and Δ2ΔFosB 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 fosBd alleles, the latter exclusively encoding ΔFosB/Δ2ΔFosB. 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 ΔFosB/Δ2ΔFosB-dependent manner. We furthermore found that mRNAs for basement membrane proteins were significantly up-regulated in fosBd/d but not fosB-null mutant cells, whereas genes involved in the TGF-β1 signaling pathway were up-regulated in both mutants. Cell-matrix adhesion was remarkably augmented in fosBd/d ES cells and to some extent in fosB-null cells. By analyzing ES cell lines carrying homozygous fosBFN alleles, which exclusively encode FosB, we confirmed that FosB negatively regulates cell-matrix adhesion and the TGF-β1 signaling pathway. We thus concluded that FosB and ΔFosB/Δ2ΔFosB use this pathway to antagonistically regulate cell matrix adhesion.

Original languageEnglish
Pages (from-to)4717-4729
Number of pages13
JournalMolecular biology of the cell
Volume19
Issue number11
DOIs
Publication statusPublished - Nov 2008

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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