Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 488164
Title Systemic Regulation of RAS/MAPK Signaling by the Serotonin Metabolite 5-HIAA
Author(s) Schmid, T.; Snoek, L.B.; Fröhli, E.; Bent, M.L. van der; Kammenga, J.E.; Hajnal, A.
Source Plos Genetics 11 (2015)5. - ISSN 1553-7404 - 16 p.
DOI https://doi.org/10.1371/journal.pgen.1005236
Department(s) Laboratory of Nematology
PE&RC
Publication type Refereed Article in a scientific journal
Publication year 2015
Keyword(s) caenorhabditis-elegans - c-elegans - natural variation - vulvar induction - complex disease - receptor - protein - gene - kinase - activation
Abstract Human cancer is caused by the interplay of mutations in oncogenes and tumor suppressor genes and inherited variations in cancer susceptibility genes. While many of the tumor initiating mutations are well characterized, the effect of genetic background variation on disease onset and progression is less understood. We have used C. elegans genetics to identify genetic modifiers of the oncogenic RAS/MAPK signaling pathway. Quantitative trait locus analysis of two highly diverged C. elegans isolates combined with allele swapping experiments identified the polymorphic monoamine oxidase A (MAOA) gene amx-2 as a negative regulator of RAS/MAPK signaling. We further show that the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), which is a product of MAOA catalysis, systemically inhibits RAS/MAPK signaling in different organs of C. elegans. Thus, MAOA activity sets a global threshold for MAPK activation by controlling 5-HIAA levels. To our knowledge, 5-HIAA is the first endogenous small molecule that acts as a systemic inhibitor of RAS/MAPK signaling.
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