DAF-16-dependent and independent expression targets of DAF-2 insulin receptor-like pathway in Caenorhabditis elegans include FKBPs.
The daf-2 insulin-like receptor pathway regulates development and life-span in Caenorhabditis elegans. Reduced DAF-2 signaling leads to changes in downstream targets via the daf-16 gene, a fork-head transcription factor which is regulated by DAF-2, and results in extended life-span. Here, we describe the first identification of genes whose expression is controlled by the DAF-2 signaling cascade. dao-1, dao-2, dao-3, dao-4, dao-8 and dao-9 are down-regulated in daf-2 mutant adults compared to wild-type adults, whereas dao-5, dao-6 and dao-7 are up-regulated. The latter genes are negatively regulated by DAF-2 signaling and positively regulated by DAF-16. Positive regulation by DAF-2 on dao-1, dao-4 and dao-8 was mediated by DAF-16, whereas daf-16 mediates only part of DAF-2 signaling for dao-2 and dao-9. Regulation by DAF-2 is most likely DAF-16 independent for dao-3 and hsp-90. RNA levels of dao-5 and dao-6 showed elevated expression in daf-2 adults, as well as being strongly expressed in dauer larvae. In contrast, hsp-90 transcript levels are low in daf-2 mutant adults though they are enriched in dauer larvae, indicating overlapping but not identical mechanisms of efficient life maintenance in stress-resistant dauer larvae and long-lived daf-2 mutant adults. dao-1, dao-8 and dao-9 are homologs of the FK506 binding proteins that interact with the mammalian insulin pathway. dao-3 encodes a putative methylenetetrahydrofolate dehydrogenase. DAO-5 shows 33 % identity with human nucleolar phosphoprotein P130. dao-7 is similar to the mammalian ZFP36 protein. Distinct regulatory patterns of dao genes implicate their diverse positions within the signaling network of DAF-2 pathway, and suggest they have unique contributions to development, metabolism and longevity.
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Molecular Biology Program and Division of Biogerontology, University of Southern California, Los Angeles, CA 90089, USA.
Larsen
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D000375:Aging / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D051858:Forkhead Transcription Factors; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017238:Genes, Helminth / Q000235:genetics*; D007814:Larva / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009154:Mutation / Q000235:genetics; D012330:RNA, Double-Stranded / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D015398:Signal Transduction; D022021:Tacrolimus Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D022021:Tacrolimus Binding Proteins