Coordination of cell proliferation and cell fate determination by CES-1 snail
| Autor: | Nadin Memar, Barbara Conradt, Bo Yan, Julia Gallinger |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
lcsh:QH426-470 Carcinogenesis Cellular differentiation Cyclin A Apoptosis Cell fate determination Neuroblast division Neuroblast Cell polarity Genetics Animals Humans cdc25 Phosphatases Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Genetics (clinical) Ecology Evolution Behavior and Systematics Heat-Shock Proteins Cell Proliferation Mammals biology Cell growth Cell Cycle fungi Cell Polarity Cell Differentiation Cell cycle Cell biology DNA-Binding Proteins Repressor Proteins lcsh:Genetics biology.protein Transcription Factors Research Article |
| Zdroj: | PLoS Genetics, Vol 9, Iss 10, p e1003884 (2013) PLoS Genetics |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | 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. Author Summary Animal development is a complex process and requires the coordination in space and time of various processes. These processes include the controlled production of cells, also referred to as ‘cell proliferation’, and the adoption by cells of specific fates, also referred to as ‘cell fate determination’. The observation that uncontrolled cell proliferation and cell fate determination contribute to conditions such as cancer, demonstrates that a precise coordination of these processes is not only important for development but for the prevention of disease throughout life. Snail-related transcription factors have previously been shown to be involved in the regulation of cell proliferation and cell fate determination. For example, the Caenorhabditis elegans Snail-related protein CES-1 affects cell fate determination in a specific cell lineage, the NSM (neurosecretory motorneuron) lineage. We now present evidence that CES-1 also controls cell proliferation in this lineage. Within a short period of time, CES-1 therefore coordinates cell proliferation and cell fate determination in one and the same lineage. Based on this finding, we propose that CES-1 is an important coordinator that is involved in the precise control - in space (NSM lineage) and time ( |
| Databáze: | OpenAIRE |
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