| First Author | Ohnishi YN | Year | 2008 |
| Journal | Mol Biol Cell | Volume | 19 |
| Issue | 11 | Pages | 4717-29 |
| PubMed ID | 18753407 | Mgi Jnum | J:220449 |
| Mgi Id | MGI:5634798 | Doi | 10.1091/mbc.E07-08-0768 |
| Citation | Ohnishi YN, et al. (2008) Antagonistic regulation of cell-matrix adhesion by FosB and DeltaFosB/Delta2DeltaFosB encoded by alternatively spliced forms of fosB transcripts. Mol Biol Cell 19(11):4717-29 |
| abstractText | 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. |
