Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of Caenorhabditis elegans.

In Caenorhabditis elegans (C. elegans), the promotion of longevity by the transcription factor DAF-16 requires reduced insulin/IGF receptor (IIR) signaling or the ablation of the germline, although the reason for the negative impact of germ cells is unknown. FOXO/DAF-16 activity inhibits germline pr...

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Main Authors: Wenjing Qi, Xu Huang, Elke Neumann-Haefelin, Ekkehard Schulze, Ralf Baumeister
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002836&type=printable
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author Wenjing Qi
Xu Huang
Elke Neumann-Haefelin
Ekkehard Schulze
Ralf Baumeister
author_facet Wenjing Qi
Xu Huang
Elke Neumann-Haefelin
Ekkehard Schulze
Ralf Baumeister
author_sort Wenjing Qi
collection DOAJ
description In Caenorhabditis elegans (C. elegans), the promotion of longevity by the transcription factor DAF-16 requires reduced insulin/IGF receptor (IIR) signaling or the ablation of the germline, although the reason for the negative impact of germ cells is unknown. FOXO/DAF-16 activity inhibits germline proliferation in both daf-2 mutants and gld-1 tumors. In contrast to its function as a germline tumor suppressor, we now provide evidence that somatic DAF-16 in the presence of IIR signaling can also result in tumorigenic activity, which counteracts robust lifespan extension. In contrast to the cell-autonomous IIR signaling, which is required for larval germline proliferation, activation of DAF-16 in the hypodermis results in hyperplasia of the germline and disruption of the surrounding basement membrane. SHC-1 adaptor protein and AKT-1 kinase antagonize, whereas AKT-2 and SGK-1 kinases promote, this cell-nonautonomous DAF-16 function. Our data suggest that a functional balance of DAF-16 activities in different tissues determines longevity and reveals a novel, cell-nonautonomous role of FOXO/DAF-16 to affect stem cells.
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publishDate 2012-01-01
publisher Public Library of Science (PLoS)
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series PLoS Genetics
spelling doaj-art-37e82d138d914a6bb0205fb3c856f2032025-08-20T02:15:19ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-0188e100283610.1371/journal.pgen.1002836Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of Caenorhabditis elegans.Wenjing QiXu HuangElke Neumann-HaefelinEkkehard SchulzeRalf BaumeisterIn Caenorhabditis elegans (C. elegans), the promotion of longevity by the transcription factor DAF-16 requires reduced insulin/IGF receptor (IIR) signaling or the ablation of the germline, although the reason for the negative impact of germ cells is unknown. FOXO/DAF-16 activity inhibits germline proliferation in both daf-2 mutants and gld-1 tumors. In contrast to its function as a germline tumor suppressor, we now provide evidence that somatic DAF-16 in the presence of IIR signaling can also result in tumorigenic activity, which counteracts robust lifespan extension. In contrast to the cell-autonomous IIR signaling, which is required for larval germline proliferation, activation of DAF-16 in the hypodermis results in hyperplasia of the germline and disruption of the surrounding basement membrane. SHC-1 adaptor protein and AKT-1 kinase antagonize, whereas AKT-2 and SGK-1 kinases promote, this cell-nonautonomous DAF-16 function. Our data suggest that a functional balance of DAF-16 activities in different tissues determines longevity and reveals a novel, cell-nonautonomous role of FOXO/DAF-16 to affect stem cells.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002836&type=printable
spellingShingle Wenjing Qi
Xu Huang
Elke Neumann-Haefelin
Ekkehard Schulze
Ralf Baumeister
Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of Caenorhabditis elegans.
PLoS Genetics
title Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of Caenorhabditis elegans.
title_full Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of Caenorhabditis elegans.
title_fullStr Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of Caenorhabditis elegans.
title_full_unstemmed Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of Caenorhabditis elegans.
title_short Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of Caenorhabditis elegans.
title_sort cell nonautonomous signaling of foxo daf 16 to the stem cells of caenorhabditis elegans
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002836&type=printable
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