Warts Is Required for PI3K-Regulated Growth Arrest, Autophagy, and Autophagic Cell Death in Drosophila
| Autor: | Eric H. Baehrecke, Sudeshna Dutta |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Programmed cell death
Atg1 Cell Cycle Proteins DEVBIO CELLCYCLE Biology Salivary Glands Article General Biochemistry Genetics and Molecular Biology Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine stomatognathic system Autophagy medicine Animals Drosophila Proteins PI3K/AKT/mTOR pathway 030304 developmental biology 0303 health sciences Agricultural and Biological Sciences(all) Salivary gland Biochemistry Genetics and Molecular Biology(all) Cell growth TOR Serine-Threonine Kinases Tumor Suppressor Proteins fungi Intracellular Signaling Peptides and Proteins Nuclear Proteins YAP-Signaling Proteins Cell cycle Cell biology body regions MicroRNAs medicine.anatomical_structure SIGNALING Caspases Insulin Receptor Substrate Proteins Trans-Activators Drosophila Signal transduction General Agricultural and Biological Sciences Protein Kinases 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Current Biology. 18:1466-1475 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2008.08.052 |
| Popis: | Summary Background Cell growth arrest and autophagy are required for autophagic cell death in Drosophila . Maintenance of growth by expression of either activated Ras, Dp110, or Akt is sufficient to inhibit autophagy and cell death in Drosophila salivary glands, but the mechanism that controls growth arrest is unknown. Although the Warts (Wts) tumor suppressor is a critical regulator of tissue growth in animals, it is not clear how this signaling pathway controls cell growth. Results Here, we show that genes in the Wts pathway are required for salivary gland degradation and that wts mutants have defects in cell growth arrest, caspase activity, and autophagy. Expression of Atg1, a regulator of autophagy, in salivary glands is sufficient to rescue wts mutant salivary gland destruction. Surprisingly, expression of Yorkie (Yki) and Scalloped (Sd) in salivary glands fails to phenocopy wts mutants. By contrast, misexpression of the Yki target bantam was able to inhibit salivary gland cell death, even though mutations in bantam fail to suppress the wts mutant salivary gland-persistence phenotype. Significantly, wts mutant salivary glands possess altered phosphoinositide signaling, and decreased function of the class I PI3K-pathway genes chico and TOR suppressed wts defects in cell death. Conclusions Although we have previously shown that salivary gland degradation requires genes in the Wts pathway, this study provides the first evidence that Wts influences autophagy. Our data indicate that the Wts-pathway components Yki, Sd, and bantam fail to function in salivary glands and that Wts regulates salivary gland cell death in a PI3K-dependent manner. |
| Databáze: | OpenAIRE |
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