Systemic Regulation of RAS/MAPK Signaling by the Serotonin Metabolite 5-HIAA

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Mutations that activate a RAS oncogene are found in a large proportion of human cancers. In this study, we have used the roundworm Caenorhabditis elegans (C. elegans) as a model to investigate how the genetic composition of the animal affects the outcome of oncogenic RAS mutations that activate the MAPK pathway. By comparing the effects of activated RAS/MAPK signaling in two genetically different C. elegans strains, we have identified the monoamine oxidase A (MAOA) gene amx-2 as a negative regulator of RAS/MAPK signaling. MAOA enzymes are primarily known to catalyze the degradation of the neurotransmitters dopamine and serotonin. Here, we show that a specific serotonin degradation product that is produced by MAOA (5-HIAA) inhibits RAS signaling in different organs of C. elegans. Thus, by producing the inhibitory serotonin metabolite 5-HIAA the MAOA enzyme systemically controls the activation of the RAS/MAPK pathway.

Vyšlo v časopise: Systemic Regulation of RAS/MAPK Signaling by the Serotonin Metabolite 5-HIAA. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005236
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005236

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