PIG-1 MELK-dependent phosphorylation of nonmuscle myosin II promotes apoptosis through CES-1 Snail partitioning

English version

Autoři: Hai Wei ^aff001; Eric J. Lambie ^aff001; Daniel S. Osório ^aff003; Ana X. Carvalho ^aff003; Barbara Conradt ^aff001
Působiště autorů: Department Biology II, Faculty of Biology, Ludwig-Maximilians-University Munich, Großhadener, Planegg-Martinsried, Germany ^aff001; Research Department of Cell and Developmental Biology, Division of Biosciences, University College London, Gower Street, London WC1E 6BT, United Kingdom ^aff002; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal ^aff003; CIPSM–Center for Integrated Protein Science Munich, Butenandtstraße, München, Germany ^aff004
Vyšlo v časopise: PIG-1 MELK-dependent phosphorylation of nonmuscle myosin II promotes apoptosis through CES-1 Snail partitioning. PLoS Genet 16(9): e32767. doi:10.1371/journal.pgen.1008912
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008912

Souhrn

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.

Klíčová slova:

Apoptosis – Caenorhabditis elegans – Cell cycle and cell division – Fluorescence imaging – Metaphase – Myosins – Neuroblasts – Phosphorylation

Zdroje

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