RESUMO
p63, known to play a role in development, has more recently also been implicated in cancer progression. Mutations in p63 have been shown to be responsible for several human developmental diseases. Differential splicing of the p63 gene gives rise to p63 isoforms, which can act either as tumor suppressors or as oncogene. In this report, we studied the effects of naturally occurring TAp63gamma mutants on the regulation of p53/p63 and p63 specific target genes. We observed significant differences among p63 mutants to regulate the p53/p63 and p63 specific target genes. Additionally, we observed a differential effect of p63 mutants on wildtype-p63-mediated induction of p53/p63 and p63 specific target genes. We also demonstrated that these mutants differentially regulate the binding of wildtype p63 to the promoter of target genes. Furthermore, the effects of these mutants on cell death and survival were consistent with their ability to regulate the downstream targets when compared to wildtype TAp63gamma. In summary, our data demonstrate that p63 mutants exhibit differential effects on p63 and p53/p63 specific target genes and on the induction of apoptosis, and provide further insight into the function of p63.
Assuntos
Transativadores/metabolismo , Ativação Transcricional , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Apoptose , Proteínas Hedgehog/metabolismo , Humanos , Mutação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Splicing de RNA , Transativadores/genética , Fatores de Transcrição , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
Silk is an attractive biomaterial for use in tissue engineering applications because of its slow degradation, excellent mechanical properties, and biocompatibility. In this report, we demonstrate a simple method to cast patterned films directly from silk fibroin dissolved in an ionic liquid. The films cast from the silk ionic liquid solution were found to support normal cell proliferation and differentiation. The versatility of the silk ionic liquid solutions and the ability to process large amounts of silk into materials with controlled surface topography directly from the dissolved silk ionic liquid solution could enhance the desirability of biomaterials such as silk for a variety of applications.