RESUMO
Cell competition is a conserved mechanism that regulates organ size and shares properties with the early stages of cancer. In Drosophila, wing cells with increased Myc or with optimum ribosome function become supercompetitors that kill their wild-type neighbors (called losers) up to several cell diameters away. Here, we report that modulating STAT activity levels regulates competitor status. Cells lacking STAT become losers that are killed by neighboring wild-type cells. By contrast, cells with hyper-activated STAT become supercompetitors that kill losers located at a distance in a manner that is dependent on hid but independent of Myc, Yorkie, Wingless signaling, and of ribosome biogenesis. These results indicate that STAT, Wingless and Myc are major parallel regulators of cell competition, which may converge on signals that non-autonomously kill losers. As hyper-activated STATs are causal to tumorigenesis and stem cell niche occupancy, our results have therapeutic implications for cancer and regenerative medicine.
Assuntos
Proteínas de Drosophila/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ribossomos/metabolismo , Fatores de Transcrição STAT/metabolismo , Transativadores/metabolismo , Proteína Wnt1/metabolismo , Animais , Drosophila , Proteínas de Drosophila/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas c-myc/genética , Fatores de Transcrição STAT/genética , Transativadores/genética , Proteína Wnt1/genética , Proteínas de Sinalização YAPRESUMO
PTL-1, a microtubule-associated protein of the structural MAP2/tau family, is the sole member of this gene family in Caenorhabditis elegans. Sequence analysis of available invertebrate genomes revealed a number of single, putative tau-like genes with high similarity to ptl-1. The ptl-1 gene is expressed in a number of cells, most notably mechanosensory neurons. We examined the role of ptl-1 in C. elegans in adult neurons as well as during development. A ptl-1 knockout strain of worms exhibited an egg-hatching defect, as well as a reduced sensitivity to touch stimuli. In addition, the knockout allele ptl-1(ok621) acts as a dominant enhancer of several temperature-sensitive alleles of mec-7 and mec-12, which code the isoforms of beta-tubulin and alpha-tubulin that together form the unusual 15 protofilament microtubules involved in touch sensation. These results demonstrate for the first time a functional role for this microtubule-associated protein in nematodes and suggest that PTL-1 is involved in mechanosensation as well as some aspect of embryogenesis.