Antagonistic Regulation of Cell-Matrix Adhesion by FosB and ΔFosB/Δ2ΔFosB Encoded by Alternatively Spliced Forms of fosB Transcripts

被引:14
作者
Ohnishi, Yoshinori N. [1 ]
Sakumi, Kunihiko [1 ]
Yamazaki, Katsuhisa [1 ]
Ohnishi, Yoko H. [1 ]
Miura, Tomofumi [1 ]
Tominaga, Yohei [1 ]
Nakabeppu, Yusaku [1 ]
机构
[1] Kyushu Univ, Med Inst Bioregulat, Dept Immunobiol & Neurosci, Div Neurofunct Genom, Fukuoka 8128582, Japan
基金
日本科学技术振兴机构; 日本学术振兴会;
关键词
D O I
10.1091/mbc.E07-08-0768
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Among fos family genes encoding components of activator protein-1 complex, only the fosB gene produces two forms of mature transcripts, namely fosB and Delta fosB mRNAs, by alternative splicing of an exonic intron. The former encodes full-length FosB. The latter encodes Delta FosB and Delta 2 Delta FosB 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 Delta FosB/Delta 2 Delta FosB. 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 Delta FosB/Delta 2 Delta FosB-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-beta 1 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-beta 1 signaling pathway. We thus concluded that FosB and Delta FosB/Delta 2 Delta FosB use this pathway to antagonistically regulate cell matrix adhesion.
引用
收藏
页码:4717 / 4729
页数:13
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