A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans.
The PTEN tumour suppressor encodes a phosphatase, and its daf-18 orthologue in Caenorhabditis elegans negatively regulates the insulin/IGF-1 DAF-2 receptor pathway that influences lifespan in worms and other species. In order to identify new DAF-18 regulated pathways involved in aging, we initiated...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2556085?pdf=render |
| _version_ | 1811268656833757184 |
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| author | Ingrid Masse Laurent Molin Laurent Mouchiroud Philippe Vanhems Francesca Palladino Marc Billaud Florence Solari |
| author_facet | Ingrid Masse Laurent Molin Laurent Mouchiroud Philippe Vanhems Francesca Palladino Marc Billaud Florence Solari |
| author_sort | Ingrid Masse |
| collection | DOAJ |
| description | The PTEN tumour suppressor encodes a phosphatase, and its daf-18 orthologue in Caenorhabditis elegans negatively regulates the insulin/IGF-1 DAF-2 receptor pathway that influences lifespan in worms and other species. In order to identify new DAF-18 regulated pathways involved in aging, we initiated a candidate RNAi feeding screen for clones that lengthen lifespan. Here, we report that smg-1 inactivation increases average lifespan in a daf-18 dependent manner. Genetic analysis is consistent with SMG-1 acting at least in part in parallel to the canonical DAF-2 receptor pathway, but converging on the transcription factor DAF-16/FOXO. SMG-1 is a serine-threonine kinase which plays a conserved role in nonsense-mediated mRNA decay (NMD) in worms and mammals. In addition, human SMG-1 has also been implicated in the p53-mediated response to genotoxic stress. The effect of smg-1 inactivation on lifespan appears to be unrelated to its NMD function, but requires the p53 tumour suppressor orthologue cep-1. Furthermore, smg-1 inactivation confers a resistance to oxidative stress in a daf-18-, daf-16- and cep-1-dependent manner. We propose that the role of SMG-1 in lifespan regulation is at least partly dependent on its function in oxidative stress resistance. Taken together, our results unveil a novel role for SMG-1 in lifespan regulation. |
| first_indexed | 2024-04-12T21:26:45Z |
| format | Article |
| id | doaj.art-7b8740aceb664f499fcc1d38a38f46f8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T21:26:45Z |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7b8740aceb664f499fcc1d38a38f46f82022-12-22T03:16:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01310e335410.1371/journal.pone.0003354A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans.Ingrid MasseLaurent MolinLaurent MouchiroudPhilippe VanhemsFrancesca PalladinoMarc BillaudFlorence SolariThe PTEN tumour suppressor encodes a phosphatase, and its daf-18 orthologue in Caenorhabditis elegans negatively regulates the insulin/IGF-1 DAF-2 receptor pathway that influences lifespan in worms and other species. In order to identify new DAF-18 regulated pathways involved in aging, we initiated a candidate RNAi feeding screen for clones that lengthen lifespan. Here, we report that smg-1 inactivation increases average lifespan in a daf-18 dependent manner. Genetic analysis is consistent with SMG-1 acting at least in part in parallel to the canonical DAF-2 receptor pathway, but converging on the transcription factor DAF-16/FOXO. SMG-1 is a serine-threonine kinase which plays a conserved role in nonsense-mediated mRNA decay (NMD) in worms and mammals. In addition, human SMG-1 has also been implicated in the p53-mediated response to genotoxic stress. The effect of smg-1 inactivation on lifespan appears to be unrelated to its NMD function, but requires the p53 tumour suppressor orthologue cep-1. Furthermore, smg-1 inactivation confers a resistance to oxidative stress in a daf-18-, daf-16- and cep-1-dependent manner. We propose that the role of SMG-1 in lifespan regulation is at least partly dependent on its function in oxidative stress resistance. Taken together, our results unveil a novel role for SMG-1 in lifespan regulation.http://europepmc.org/articles/PMC2556085?pdf=render |
| spellingShingle | Ingrid Masse Laurent Molin Laurent Mouchiroud Philippe Vanhems Francesca Palladino Marc Billaud Florence Solari A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans. PLoS ONE |
| title | A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans. |
| title_full | A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans. |
| title_fullStr | A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans. |
| title_full_unstemmed | A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans. |
| title_short | A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans. |
| title_sort | novel role for the smg 1 kinase in lifespan and oxidative stress resistance in caenorhabditis elegans |
| url | http://europepmc.org/articles/PMC2556085?pdf=render |
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