Identification of a DAF-16 transcriptional target gene, scl-1, that regulates longevity and stress resistance in Caenorhabditis elegans.
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.
Ookuma
Sadatsugu
S
Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Fukuda
Makoto
M
Nishida
Eisuke
E
D000375:Aging / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors; D008136:Longevity / Q000235:genetics*; D008969:Molecular Sequence Data; D014157:Transcription Factors / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; C478038:SCL-1 protein, C elegans; D014157:Transcription Factors; C108831:daf-16 protein, C elegans