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Antagonistic regulation of cell-matrix adhesion by FosB and DeltaFosB/Delta2DeltaFosB encoded by alternatively spliced forms of fosB transcripts.
Ohnishi, Yoshinori N; Sakumi, Kunihiko; Yamazaki, Katsuhisa; Ohnishi, Yoko H; Miura, Tomofumi; Tominaga, Yohei; Nakabeppu, Yusaku.
Afiliação
  • Ohnishi YN; Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Mol Biol Cell ; 19(11): 4717-29, 2008 Nov.
Article em En | MEDLINE | ID: mdl-18753407
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas c-fos / Processamento Alternativo / Junções Célula-Matriz / Proteínas Mutantes / Mutação Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Biol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2008 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas c-fos / Processamento Alternativo / Junções Célula-Matriz / Proteínas Mutantes / Mutação Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Biol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2008 Tipo de documento: Article País de afiliação: Japão