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Caenorhabditis elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity.
Dev Biol. 2008 Mar 15; 315(2):290-302.DB

Abstract

Insulin regulates development, metabolism, and lifespan via a conserved PI3K/Akt pathway that promotes cytoplasmic sequestration of FoxO transcription factors. The regulation of nuclear FoxO is poorly understood. In the nematode Caenorhabditis elegans, insulin-like signaling functions in larvae to inhibit dauer arrest and acts during adulthood to regulate lifespan. In a screen for genes that modulate C. elegans insulin-like signaling, we identified eak-3, which encodes a novel protein that is specifically expressed in the two endocrine XXX cells. The dauer arrest phenotype of eak-3 mutants is fully suppressed by mutations in daf-16/FoxO, which encodes the major target of C. elegans insulin-like signaling, and daf-12, which encodes a nuclear receptor regulated by steroid hormones known as dafachronic acids. eak-3 mutation does not affect DAF-16/FoxO subcellular localization but enhances expression of the direct DAF-16/FoxO target sod-3 in a daf-16/FoxO- and daf-12-dependent manner. eak-3 mutants have normal lifespans, suggesting that EAK-3 decouples insulin-like regulation of development and longevity. We propose that EAK-3 activity in the XXX cells promotes the synthesis and/or secretion of a hormone that acts in parallel to AKT-1 to inhibit the expression of DAF-16/FoxO target genes. Similar hormonal pathways may regulate FoxO target gene expression in mammals.

Authors+Show Affiliations

Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18241854

Citation

Zhang, Yanmei, et al. "Caenorhabditis Elegans EAK-3 Inhibits Dauer Arrest Via Nonautonomous Regulation of Nuclear DAF-16/FoxO Activity." Developmental Biology, vol. 315, no. 2, 2008, pp. 290-302.
Zhang Y, Xu J, Puscau C, et al. Caenorhabditis elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity. Dev Biol. 2008;315(2):290-302.
Zhang, Y., Xu, J., Puscau, C., Kim, Y., Wang, X., Alam, H., & Hu, P. J. (2008). Caenorhabditis elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity. Developmental Biology, 315(2), 290-302. https://doi.org/10.1016/j.ydbio.2007.12.032
Zhang Y, et al. Caenorhabditis Elegans EAK-3 Inhibits Dauer Arrest Via Nonautonomous Regulation of Nuclear DAF-16/FoxO Activity. Dev Biol. 2008 Mar 15;315(2):290-302. PubMed PMID: 18241854.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caenorhabditis elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity. AU - Zhang,Yanmei, AU - Xu,Jinling, AU - Puscau,Cristina, AU - Kim,Yongsoon, AU - Wang,Xi, AU - Alam,Hena, AU - Hu,Patrick J, Y1 - 2008/01/03/ PY - 2007/12/07/received PY - 2007/12/11/accepted PY - 2008/2/5/pubmed PY - 2008/3/28/medline PY - 2008/2/5/entrez SP - 290 EP - 302 JF - Developmental biology JO - Dev. Biol. VL - 315 IS - 2 N2 - Insulin regulates development, metabolism, and lifespan via a conserved PI3K/Akt pathway that promotes cytoplasmic sequestration of FoxO transcription factors. The regulation of nuclear FoxO is poorly understood. In the nematode Caenorhabditis elegans, insulin-like signaling functions in larvae to inhibit dauer arrest and acts during adulthood to regulate lifespan. In a screen for genes that modulate C. elegans insulin-like signaling, we identified eak-3, which encodes a novel protein that is specifically expressed in the two endocrine XXX cells. The dauer arrest phenotype of eak-3 mutants is fully suppressed by mutations in daf-16/FoxO, which encodes the major target of C. elegans insulin-like signaling, and daf-12, which encodes a nuclear receptor regulated by steroid hormones known as dafachronic acids. eak-3 mutation does not affect DAF-16/FoxO subcellular localization but enhances expression of the direct DAF-16/FoxO target sod-3 in a daf-16/FoxO- and daf-12-dependent manner. eak-3 mutants have normal lifespans, suggesting that EAK-3 decouples insulin-like regulation of development and longevity. We propose that EAK-3 activity in the XXX cells promotes the synthesis and/or secretion of a hormone that acts in parallel to AKT-1 to inhibit the expression of DAF-16/FoxO target genes. Similar hormonal pathways may regulate FoxO target gene expression in mammals. SN - 1095-564X UR - https://www.unboundmedicine.com/medline/citation/18241854/Caenorhabditis_elegans_EAK_3_inhibits_dauer_arrest_via_nonautonomous_regulation_of_nuclear_DAF_16/FoxO_activity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0012-1606(07)01605-3 DB - PRIME DP - Unbound Medicine ER -