Direct and Indirect Gene Regulation by a Life-Extending FOXO Protein in C. elegans: Roles for GATA Factors and Lipid Gene Regulators
SCIE
SCOPUS
- Title
- Direct and Indirect Gene Regulation by a Life-Extending FOXO Protein in C. elegans: Roles for GATA Factors and Lipid Gene Regulators
- Authors
- Peichuan Zhang; Meredith Judy; Lee, SJ; Cynthia Kenyon
- Date Issued
- 2013-01-08
- Publisher
- CELL PRESS
- Abstract
- In long-lived C. elegans insulin/IGF-1 pathway mutants, the life-extending FOXO transcription factor DAF-16 is present throughout the animal, but we find that its activity in a single tissue can delay the aging of other tissues and extend the animal's life span. To better understand the topography of DAF-16 action among the tissues, we analyzed a collection of DAF-16-regulated genes. DAF-16 regulated most of these genes in a cell-autonomous fashion, often using tissue-specific GATA factors to direct their expression to specific tissues. DAF-16 could also act cell nonautonomously to influence gene expression. DAF-16 affected gene expression in other cells, at least in part, via the lipid-gene regulator MDT-15. DAF-16, and probably MDT-15, could act cell nonautonomously in the endoderm to ameliorate the paralysis caused by expressing Alzheimer's A beta protein in muscles. These findings suggest that MDT-15-dependent intercellular signals, possibly lipid signals, can help to coordinate tissue physiology, enhance proteostasis, and extend life in response to DAF-16/FOXO activity.
- Keywords
- BETA-AMYLOID PEPTIDE; CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; INSULIN-RECEPTOR; SPAN EXTENSION; FAT-BODY; DAF-16; EXPRESSION; LONGEVITY
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/14782
- DOI
- 10.1016/J.CMET.2012.12.013
- ISSN
- 1550-4131
- Article Type
- Article
- Citation
- Cell Metabolsim, vol. 17, no. 1, page. 85 - 100, 2013-01-08
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