RESUMO
The proapoptotic factors Reaper, Hid, Grim, and Sickle regulate apoptosis in Drosophila by inhibiting the antiapoptotic factor DIAP1 (Drosophila inhibitor of apoptosis 1). Heat, UV light, x-rays, and developmental signals can all increase the proapoptotic factors, but the control of transcription of the diap1 gene is unclear. We show that in imaginal discs the single Drosophila STAT protein (STAT92E) when activated can directly increase DIAP1 through binding to STAT DNA-binding sites in the diap1 promoter. The STAT92E contribution to DIAP1 production is required for cell survival after x-irradiation but not under unstressed conditions. Because DIAP1 prevents apoptosis after a variety of stresses, STAT92E may have a role in regulating stress responses in general.
Assuntos
Apoptose/efeitos da radiação , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Inibidoras de Apoptose/metabolismo , Fatores de Transcrição STAT/metabolismo , Animais , Animais Geneticamente Modificados , Sequência de Bases , Sítios de Ligação , Proteínas de Drosophila/deficiência , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/efeitos da radiação , Olho/citologia , Olho/metabolismo , Proteínas Inibidoras de Apoptose/genética , Fosforilação , Regiões Promotoras Genéticas/genética , Fatores de Transcrição STAT/deficiência , Fatores de Transcrição STAT/genéticaAssuntos
Cromatina/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas Tirosina Quinases/metabolismo , Fatores de Transcrição/metabolismo , Alelos , Animais , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Regulação da Expressão Gênica , Marcadores Genéticos , Janus Quinases , Modelos Genéticos , Mutação , Proteínas Tirosina Quinases/genética , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , Fatores de Transcrição/genéticaRESUMO
Previously unrecognized mRNAs originating from a dual promoter at the stat92E locus are described. One of these encodes a truncated protein, DeltaNSTAT92E, that lacks the N-terminal 133 amino acids. Antibodies detect both the full-length and truncated molecules early in embryogenesis (1-5 h), and mRNA detection by specific RT-PCR reactions accords with the protein distribution. Given that the N termini of mammalian STATs are known to have positive functions in transcriptional activation, we explored the role of DeltaNSTAT92E early in embryogenesis. By increasing the DeltaNSTAT92E-to-STAT92E ratio in overexpression and RNAi experiments, we observe phenotypes compatible with suppression of wild-type STAT92E activity. We therefore conclude that the short form of STAT92E is a naturally occurring dominant-negative product that can be added to the growing list of negative regulators of STAT activity.
