RESUMO
The endoplasmic reticulum (ER) has a major role in protein folding. The accumulation of unfolded proteins in the ER induces a stress, which can be resolved by the unfolded protein response (UPR). Chronicity of ER stress leads to UPR-induced apoptosis and in turn to an unbalance of tissue homeostasis. Although ER stress-dependent apoptosis is observed in a great number of devastating human diseases, how cells activate apoptosis and promote tissue homeostasis after chronic ER stress remains poorly understood. Here, using the Drosophila wing imaginal disc as a model system, we validated that Presenilin overexpression induces chronic ER stress in vivo. We observed, in this novel model of chronic ER-stress, a PERK/ATF4-dependent apoptosis requiring downregulation of the antiapoptotic diap1 gene. PERK/ATF4 also activated the JNK pathway through Rac1 and Slpr activation in apoptotic cells, leading to the expression of Dilp8. This insulin-like peptide caused a developmental delay, which partially allowed the replacement of apoptotic cells. Thanks to a novel chronic ER stress model, these results establish a new pathway that both participates in tissue homeostasis and triggers apoptosis through an original regulation.
Assuntos
Apoptose , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Estresse do Retículo Endoplasmático , Proteínas Inibidoras de Apoptose/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , MAP Quinase Quinase 4/metabolismo , MAP Quinase Quinase Quinases/metabolismo , eIF-2 Quinase/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo , Animais , Drosophila/citologia , Drosophila/genética , Proteínas de Drosophila/genética , Humanos , Proteínas Inibidoras de Apoptose/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , MAP Quinase Quinase 4/genética , MAP Quinase Quinase Quinases/genética , Modelos Animais , Presenilinas/genética , Presenilinas/metabolismo , Transdução de Sinais , Resposta a Proteínas não Dobradas , eIF-2 Quinase/genética , Proteínas rac de Ligação ao GTP/genéticaRESUMO
We describe here the use of the ISfinder database and its associated software. ISfinder was conceived -initially as a comprehensive database for prokaryotic insertion sequences (ISs). It now includes software for visualising complete and partial IS copies in whole genomes (ISbrowser) and for high-quality genome annotation (Insertion Sequence Semi-automatic Genome Annotation).
Assuntos
Elementos de DNA Transponíveis , Bases de Dados de Ácidos Nucleicos , Genoma Bacteriano , Anotação de Sequência Molecular/métodos , Software , Bactérias/genética , Sequência de Bases , Sistemas On-LineRESUMO
ISfinder (www-is.biotoul.fr) is a dedicated database for bacterial insertion sequences (ISs). It has superseded the Stanford reference center. One of its functions is to assign IS names and to provide a focal point for a coherent nomenclature. It is also the repository for ISs. Each new IS is indexed together with information such as its DNA sequence and open reading frames or potential coding sequences, the sequence of the ends of the element and target sites, its origin and distribution together with a bibliography where available. Another objective is to continuously monitor ISs to provide updated comprehensive groupings or families and to provide some insight into their phylogenies. The site also contains extensive background information on ISs and transposons in general. Online tools are gradually being added. At present an online Blast facility against the entire bank is available. But additional features will include alignment capability, PsiBLAST and HMM profiles. ISfinder also includes a section on bacterial genomes and is involved in annotating the IS content of these genomes. Finally, this database is currently recommended by several microbiology journals for registration of new IS elements before their publication.
