C. elegans PTEN and AMPK block neuroblast divisions by inhibiting a BMP-insulin-PP2A-MAPK pathway
| Autor: | Brandon Lam, Ian D. Chin-Sang, Shanqing Zheng, Zhi Qu, Michael Zanetti |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway biology AMPK Protein phosphatase 2 biology.organism_classification 3. Good health Cell biology 03 medical and health sciences 030104 developmental biology Neuroblast biology.protein PTEN Protein kinase A Molecular Biology Transcription factor Caenorhabditis elegans Developmental Biology |
| Zdroj: | Development. 145 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.166876 |
| Popis: | Caenorhabditis elegans that hatch in the absence of food stop their postembryonic development in a process called L1 arrest. Intriguingly, we find that the postembryonic Q neuroblasts divide and migrate during L1 arrest in mutants that have lost the energy sensor AMP-activated protein kinase (AMPK) or the insulin/IGF-1 signaling (IIS) negative regulator DAF-18/PTEN. We report that DBL-1/BMP works upstream of IIS to promote agonistic insulin-like peptides during L1 arrest. However, the abnormal Q cell divisions that occur during L1 arrest use a novel branch of the IIS pathway that is independent of the terminal transcription factor DAF-16/FOXO. Using genetic epistasis and drug interactions we show that AMPK functions downstream of, or in parallel with DAF-18/PTEN and IIS to inhibit PP2A function. Further, we show that PP2A regulates the abnormal Q cell divisions by activating the MPK-1/ERK signaling pathway via LIN-45/RAF, independently of LET-60/RAS. PP2A acts as a tumor suppressor in many oncogenic signaling cascades. Our work demonstrates a new role for PP2A that is needed to induce neuroblast divisions during starvation and is regulated by both insulin and AMPK. |
| Databáze: | OpenAIRE |
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