RESUMO
Btg2 is a primary p53 transcriptional target gene which may function as a coactivator-corepressor and/or an adaptor molecule that modulates the activities of its interacting proteins. We have generated Btg2-null mice to elucidate the in vivo function of Btg2. Btg2-null mice are viable and fertile but exhibit posterior homeotic transformations of the axial vertebrae in a dose-dependent manner. Consistent with its role in vertebral patterning, Btg2 is expressed in the presomitic mesoderm, tail bud, and somites during somitogenesis. We further provide biochemical evidence that Btg2 interacts with bone morphogenetic protein (BMP)-activated Smads and enhances the transcriptional activity of BMP signaling. In view of the genetic evidence that reduced BMP signaling causes posteriorization of the vertebral pattern, we propose that the observed vertebral phenotype in Btg2-null mice is due to attenuated BMP signaling.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Genes Supressores de Tumor/fisiologia , Proteínas Imediatamente Precoces/fisiologia , Transdução de Sinais , Transativadores/metabolismo , Transcrição Gênica , Proteína Supressora de Tumor p53/metabolismo , Alelos , Animais , Southern Blotting , Padronização Corporal , Linhagem Celular , Relação Dose-Resposta a Droga , Embrião de Mamíferos/citologia , Éxons , Feminino , Genes Reporter , Vetores Genéticos , Humanos , Proteínas Imediatamente Precoces/genética , Immunoblotting , Imunoprecipitação , Hibridização In Situ , Masculino , Camundongos , Camundongos Transgênicos , Modelos Genéticos , Mutação , RNA Mensageiro/metabolismo , Proteínas Smad , Células-Tronco/metabolismo , Transfecção , Proteínas Supressoras de TumorRESUMO
We report in this study that an oxoiron(IV) porphyrin complex bearing electron-deficient porphyrin ligand, (TPFPP)FeIV=O (TPFPP = meso-tetrakis(pentafluorophenyl)porphinato dianion), shows reactivities similar to those found in oxoiron(IV) porphyrin pi-cation radicals. In the epoxidation of olefins by the (TPFPP)FeIV=O complex, epoxides were yielded as major products; cyclohexene oxide was the sole product formed in the epoxidation of cyclohexene, and stilbenes were stereospecifically oxidized to the corresponding epoxide products. More striking results were obtained in alkane hydroxylation reactions; the hydroxylation of adamantane afforded a high degree of selectivity for tertiary C-H bonds over secondary C-H bonds, and the hydroxylation of cis-1,2-dimethylcyclohexane yielded a tertiary alcohol product with >99% retention of stereochemistry. The latter result demonstrates that an oxoiron(IV) porphyrin complex hydroxylates alkanes with a high stereospecificity. Isotope labeling studies performed with H218O and 18O2 in the olefin epoxidation and alkane hydroxylation reactions demonstrated that oxygen atoms in oxygenated products derived from the oxoiron(IV) porphyrin complex.