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 language | English |
|---|---|
| Pages (from-to) | 4717-4729 |
| Number of pages | 13 |
| Journal | Molecular biology of the cell |
| Volume | 19 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2008 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology
Cite this
Antagonistic regulation of cell-matrix adhesion by FosB and ΔFosB/Δ2ΔFosB encoded by alternatively spliced forms of fosB transcripts. / Ohnishi, Yoshinori N.; Sakumi, Kunihiko; Yamazaki, Katsuhisa; Ohnishi, Yoko H.; Miura, Tomofumi; Tominaga, Yohei; Nakabeppu, Yusaku.
In: Molecular biology of the cell, Vol. 19, No. 11, 01.11.2008, p. 4717-4729.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antagonistic regulation of cell-matrix adhesion by FosB and ΔFosB/Δ2ΔFosB encoded by alternatively spliced forms of fosB transcripts
AU - Ohnishi, Yoshinori N.
AU - Sakumi, Kunihiko
AU - Yamazaki, Katsuhisa
AU - Ohnishi, Yoko H.
AU - Miura, Tomofumi
AU - Tominaga, Yohei
AU - Nakabeppu, Yusaku
PY - 2008/11/1
Y1 - 2008/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=58149277722&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58149277722&partnerID=8YFLogxK
U2 - 10.1091/mbc.E07-08-0768
DO - 10.1091/mbc.E07-08-0768
M3 - Article
C2 - 18753407
AN - SCOPUS:58149277722
VL - 19
SP - 4717
EP - 4729
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 11
ER -