論文 - 詳細
| RRC ID | 65313 |
|---|---|
| 著者 | Wei H, Lambie EJ, Osório DS, Carvalho AX, Conradt B. |
| タイトル | PIG-1 MELK-dependent phosphorylation of nonmuscle myosin II promotes apoptosis through CES-1 Snail partitioning. |
| ジャーナル | PLoS Genet |
| Abstract |
The mechanism(s) through which mammalian kinase MELK promotes tumorigenesis is not understood. We find that the C. elegans orthologue of MELK, PIG-1, promotes apoptosis by partitioning an anti-apoptotic factor. The C. elegans NSM 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 MELK is required for partitioning of CES-1 Snail, a transcriptional repressor of the pro-apoptotic gene egl-1 BH3-only. pig-1 MELK is controlled by both a ces-1 Snail- and par-4 LKB1-dependent pathway, and may act through phosphorylation and cortical enrichment of nonmuscle myosin II prior to neuroblast division. We propose that pig-1 MELK-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 which ces-1 Snail controls its own activity through the formation of a gradient of CES-1 Snail protein. |
| 巻・号 | 16(9) |
| ページ | e1008912 |
| 公開日 | 2020-9-1 |
| DOI | 10.1371/journal.pgen.1008912 |
| PII | PGENETICS-D-20-00874 |
| PMID | 32946434 |
| PMC | PMC7527206 |
| MeSH | Actomyosin / metabolism Animals Animals, Genetically Modified Apoptosis / physiology Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Death / physiology Cell Polarity / physiology Cytoskeletal Proteins / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Myosin Type II / metabolism Neural Stem Cells / metabolism Neurons / metabolism Phosphorylation Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Snail Family Transcription Factors / genetics Snail Family Transcription Factors / metabolism Transcription Factors / genetics Transcription Factors / metabolism* |
| リソース情報 | |
| 線虫 | tm1036 |