title: Coordination of cell proliferation and cell fate determination by CES-1 snail.
abstract: The coordination of cell proliferation and cell fate determination is critical during development but the mechanisms through which this is accomplished are unclear. We present evidence that the Snail-related transcription factor CES-1 of Caenorhabditis elegans coordinates these processes in a specific cell lineage. CES-1 can cause loss of cell polarity in the NSM neuroblast. By repressing the transcription of the BH3-only gene egl-1, CES-1 can also suppress apoptosis in the daughters of the NSM neuroblasts. We now demonstrate that CES-1 also affects cell cycle progression in this lineage. Specifically, we found that CES-1 can repress the transcription of the cdc-25.2 gene, which encodes a Cdc25-like phosphatase, thereby enhancing the block in NSM neuroblast division caused by the partial loss of cya-1, which encodes Cyclin A. Our results indicate that CDC-25.2 and CYA-1 control specific cell divisions and that the over-expression of the ces-1 gene leads to incorrect regulation of this functional 'module'. Finally, we provide evidence that dnj-11 MIDA1 not only regulate CES-1 activity in the context of cell polarity and apoptosis but also in the context of cell cycle progression. In mammals, the over-expression of Snail-related genes has been implicated in tumorigenesis. Our findings support the notion that the oncogenic potential of Snail-related transcription factors lies in their capability to, simultaneously, affect cell cycle progression, cell polarity and apoptosis and, hence, the coordination of cell proliferation and cell fate determination.
authors.affiliation: Center for Integrated Protein Science, Department of Biology II, Ludwig-Maximilians-University, Munich, Planegg-Martinsried, Germany ; Department of Genetics, MCB Graduate Program, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.forename: Nadin
authors.initials: N
authors.lastname: Memar
authors.forename: Julia
authors.initials: J
authors.lastname: Gallinger
authors.forename: Barbara
authors.initials: B
authors.lastname: Conradt
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D016764:Cell Polarity / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D019925:Cyclin A / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008322:Mammals; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D019925:Cyclin A; D004268:DNA-Binding Proteins; C530133:Dnj-11 protein, C elegans; C112486:EGL-1 protein, C elegans; D006360:Heat-Shock Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C121976:ces-1 protein, C elegans; C533900:CDC-25.1 protein, C elegans; D020687:cdc25 Phosphatases