Positive feedback between transcriptional and kinase suppression in nematodes with extraordinary longevity and stress resistance.
| Autor: | Cagdaş Tazearslan, Srinivas Ayyadevara, Puneet Bharill, Robert J Shmookler Reis |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | PLoS Genetics, Vol 5, Iss 4, p e1000452 (2009) |
| Druh dokumentu: | article |
| ISSN: | 1553-7390 1553-7404 |
| DOI: | 10.1371/journal.pgen.1000452 |
| Popis: | Insulin/IGF-1 signaling (IIS) regulates development and metabolism, and modulates aging, of Caenorhabditis elegans. In nematodes, as in mammals, IIS is understood to operate through a kinase-phosphorylation cascade that inactivates the DAF-16/FOXO transcription factor. Situated at the center of this pathway, phosphatidylinositol 3-kinase (PI3K) phosphorylates PIP(2) to form PIP(3), a phospholipid required for membrane tethering and activation of many signaling molecules. Nonsense mutants of age-1, the nematode gene encoding the class-I catalytic subunit of PI3K, produce only a truncated protein lacking the kinase domain, and yet confer 10-fold greater longevity on second-generation (F2) homozygotes, and comparable gains in stress resistance. Their F1 parents, like weaker age-1 mutants, are far less robust-implying that maternally contributed trace amounts of PI3K activity or of PIP(3) block the extreme age-1 phenotypes. We find that F2-mutant adults have |
| Databáze: | Directory of Open Access Journals |
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