PIG-1 MELK-dependent phosphorylation of nonmuscle myosin II promotes apoptosis through CES-1 Snail partitioning
| العنوان: | PIG-1 MELK-dependent phosphorylation of nonmuscle myosin II promotes apoptosis through CES-1 Snail partitioning |
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| المؤلفون: | Ana Carvalho, Eric J. Lambie, Hai Wei, Daniel S. Osorio, Barbara Conradt |
| المساهمون: | Instituto de Investigação e Inovação em Saúde |
| المصدر: | PLoS Genetics, Vol 16, Iss 9, p e1008912 (2020) PLoS Genetics |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cancer Research, DNA-Binding Proteins / genetics, Cell, Apoptosis, Neural Stem Cells / metabolism, Snail, Cell Polarity / physiology, QH426-470, medicine.disease_cause, Myosin Type II / metabolism, Animals, Genetically Modified, 0302 clinical medicine, Neural Stem Cells, Cytoskeletal Proteins / metabolism, Phosphorylation, Genetics (clinical), Caenorhabditis elegans, Neurons, 0303 health sciences, Cell Death, biology, Kinase, Chemistry, Neurons / metabolism, Cell Polarity, Actomyosin, Protein Serine-Threonine Kinases / genetics, Actomyosin / metabolism, Cell biology, DNA-Binding Proteins, medicine.anatomical_structure, Protein Serine-Threonine Kinases / metabolism, Snail Family Transcription Factors / genetics, Snail Family Transcription Factors / metabolism, Context (language use), Protein Serine-Threonine Kinases, Neuroblast division, 03 medical and health sciences, Neuroblast, Transcription Factors / genetics, biology.animal, Caenorhabditis elegans Proteins / metabolism, Genetics, medicine, Animals, Cell Death / physiology, Caenorhabditis elegans Proteins, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Myosin Type II, Transcription Factors / metabolism, fungi, DNA-Binding Proteins / metabolism, biology.organism_classification, Cytoskeletal Proteins, Caenorhabditis elegans Proteins / genetics, Snail Family Transcription Factors, Apoptosis / physiology, Carcinogenesis, 030217 neurology & neurosurgery, Transcription Factors |
| الوصف: | The mechanism(s) through which mammalian kinase MELK promotes tumorigenesis is not understood. We find that theC. elegansorthologue of MELK, PIG-1, promotes apoptosis by partitioning an anti-apoptotic factor. TheC. elegansNSM neuroblast divides to produce a larger cell that differentiates into a neuron and a smaller cell that dies. We find that in this context, PIG-1 is required for partitioning of CES-1 Snail, a transcriptional repressor of the pro-apoptotic geneegl-1BH3-only.pig-1MELK is controlled by both aces-1Snail- andpar-4LKB1-dependent pathway, and may act through phosphorylation and cortical enrichment of nonmuscle myosin II prior to neuroblast division. We propose thatpig-1MELK-induced local contractility of the actomyosin network plays a conserved role in the acquisition of the apoptotic fate. Our work also uncovers an auto-regulatory loop through whichces-1Snail controls its own activity through the formation of a gradient of CES-1 Snail protein.Significance StatementApoptosis is critical for the elimination of ‘unwanted’ cells. What distinguishes wanted from unwanted cells in developing animals is poorly understood. We report that in theC. elegansNSM neuroblast lineage, the level of CES-1, a Snail-family member and transcriptional repressor of the pro-apoptotic geneegl-1, contributes to this process. In addition, we demonstrate thatC. elegansPIG-1, the orthologue of mammalian proto-oncoprotein MELK, plays a critical role in controlling CES-1Snaillevels. Specifically, during NSM neuroblast division, PIG-1MELKcontrols partitioning of CES-1Snailinto one but not the other daughter cell thereby promoting the making of one wanted and one unwanted cell. Furthermore, we present evidence that PIG-1MELKacts prior to NSM neuroblast division by locally activating the actomyosin network. |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1e89eb8b227c8d8bb6fd9f36c74a4f95Test https://doi.org/10.1101/2020.06.04.133983Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1e89eb8b227c8d8bb6fd9f36c74a4f95 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |