Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1017-1028 |
| Number of pages | 12 |
| Journal | Journal of Molecular Biology |
| Volume | 314 |
| Issue number | 5 |
| DOIs | |
| State | Published - Dec 14 2001 |
| Externally published | Yes |
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Keywords
- Aging
- Dauer formation
- Development
- Differential expression
- Regulatory network
ASJC Scopus subject areas
- Virology
Cite this
DAF-16-dependent and independent expression targets of DAF-2 insulin receptor-like pathway in Caenorhabditis elegans include FKBPs. / Yu, Hui; Larsen, Pamela L.
In: Journal of Molecular Biology, Vol. 314, No. 5, 14.12.2001, p. 1017-1028.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - DAF-16-dependent and independent expression targets of DAF-2 insulin receptor-like pathway in Caenorhabditis elegans include FKBPs
AU - Yu, Hui
AU - Larsen, Pamela L
PY - 2001/12/14
Y1 - 2001/12/14
N2 - 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.
AB - 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.
KW - Aging
KW - Dauer formation
KW - Development
KW - Differential expression
KW - Regulatory network
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UR - http://www.scopus.com/inward/citedby.url?scp=0035861993&partnerID=8YFLogxK
U2 - 10.1006/jmbi.2000.5210
DO - 10.1006/jmbi.2000.5210
M3 - Article
C2 - 11743719
AN - SCOPUS:0035861993
VL - 314
SP - 1017
EP - 1028
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 5
ER -