Authors: Ookuma S; Fukuda M; Nishida E
Abstract: In Caenorhabditis elegans, an insulin-like signaling pathway, which includes the daf-2 and age-1 genes, controls longevity and stress resistance. Downregulation of this pathway activates the forkhead transcription factor DAF-16, whose transcriptional targets are suggested to play an essential role in controlling the phenotypes governed by this pathway. We have surveyed the genes that have the DAF-16 consensus binding element (DBE) within putative regulatory regions. Here, we show that one such gene, termed scl-1, is a positive regulator of longevity and stress resistance. Expression of scl-1 is upregulated in long-lived daf-2 and age-1 mutants and is undetectable in a short-lived daf-16 mutant. SCL-1 is a putative secretory protein with an SCP domain and is homologous to the mammalian cysteine-rich secretory protein (CRISP) family. scl-1 is required for the extension of the life span of daf-2 and age-1 mutants, and downregulation of scl-1 reduces both life span and stress resistance of this animal. SCL-1, whose expression is dependent on DAF-16, is the first example of a putative secretory protein that positively regulates longevity and stress resistance.
Keywords: Aging/*genetics; Amino Acid Sequence; Animals; Base Sequence; Caenorhabditis elegans/*genetics; Caenorhabditis elegans Proteins/genetics/metabolism; Longevity/*genetics; Molecular Sequence Data; Transcription Factors/*metabolism|
Journal: Current biology : CB Volume: 13 Issue: 5 Pages: 427-31 Date: March 7, 2003 PMID: 12620193 |
Ookuma S, Fukuda M, Nishida E (2003) Identification of a DAF-16 transcriptional target gene, scl-1, that regulates longevity and stress resistance in Caenorhabditis elegans. Current biology : CB 13: 427-31.
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