fer-15;shc-1

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Genetic mutants with fer-15, shc-1 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
25
Diet
NGM
Lifespan (days)
10.5
Lifespan comparisons
Double mutant fer-15(b26);shc-1(ok198) has a lifespan of 10.5 days, while single mutant fer-15(b26) has a lifespan of 14.0 days.
Citation
View abstract
Neumann-Haefelin E et al., 2008, SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to modulate life span and stress response in C. elegans. Genes Dev. 22(19):2721-35 18832074 Click here to select all mutants from this PubMed ID in the graph
Abstract
Correlative evidence links stress, accumulation of oxidative cellular damage, and aging in several species. Genetic studies in species ranging from yeast to mammals revealed several pathways regulating stress response and life span, including caloric intake, mitochondrial respiration, insulin/IGF-1 (IIS), and JNK (c-Jun N-terminal kinase) signaling. How IIS and JNK signaling cross-talk to defend against diverse stressors contributing to aging is of critical importance but, so far, only poorly understood. In this study, we demonstrate that the adaptor protein SHC-1, the Caenorhabditis elegans homolog of human p52Shc, coordinates mechanisms of stress response and aging. Using genetic and biochemical approaches, we discover that SHC-1 not only opposes IIS but also activates JNK signaling. Loss of shc-1 function results in accelerated aging and enhanced sensitivity to heat, oxidative stress, and heavy metals, whereas expression of human p52Shc rescues the shc-1 mutant phenotype. SHC-1 acts upstream of the insulin/IGF receptor DAF-2 and the PI3 kinase AGE-1 and directly interacts with DAF-2. Moreover, SHC-1 activates JNK signaling by binding to MEK-1 kinase. Both aspects converge on controlling the nuclear translocation and activation of the FOXO transcription factor DAF-16. Our findings establish C. elegans SHC-1 as a critical scaffold that directly cross-connects the two parallel JNK and IIS pathways and help to explain how these signaling cascades cooperate to ascertain normal stress response and life span in C. elegans.

Temperature °C
25
Diet
NGM
Lifespan (days)
10.7
Lifespan comparisons
Double mutant fer-15(b26);shc-1(ok198) has a lifespan of 10.7 days, while single mutant fer-15(b26) has a lifespan of 13.0 days.
Citation
View abstract
Neumann-Haefelin E et al., 2008, SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to modulate life span and stress response in C. elegans. Genes Dev. 22(19):2721-35 18832074 Click here to select all mutants from this PubMed ID in the graph
Abstract
Correlative evidence links stress, accumulation of oxidative cellular damage, and aging in several species. Genetic studies in species ranging from yeast to mammals revealed several pathways regulating stress response and life span, including caloric intake, mitochondrial respiration, insulin/IGF-1 (IIS), and JNK (c-Jun N-terminal kinase) signaling. How IIS and JNK signaling cross-talk to defend against diverse stressors contributing to aging is of critical importance but, so far, only poorly understood. In this study, we demonstrate that the adaptor protein SHC-1, the Caenorhabditis elegans homolog of human p52Shc, coordinates mechanisms of stress response and aging. Using genetic and biochemical approaches, we discover that SHC-1 not only opposes IIS but also activates JNK signaling. Loss of shc-1 function results in accelerated aging and enhanced sensitivity to heat, oxidative stress, and heavy metals, whereas expression of human p52Shc rescues the shc-1 mutant phenotype. SHC-1 acts upstream of the insulin/IGF receptor DAF-2 and the PI3 kinase AGE-1 and directly interacts with DAF-2. Moreover, SHC-1 activates JNK signaling by binding to MEK-1 kinase. Both aspects converge on controlling the nuclear translocation and activation of the FOXO transcription factor DAF-16. Our findings establish C. elegans SHC-1 as a critical scaffold that directly cross-connects the two parallel JNK and IIS pathways and help to explain how these signaling cascades cooperate to ascertain normal stress response and life span in C. elegans.

Search genes: fer-15 shc-1

Symbol
GenAge

fer-15
View on GenAge (fer-15)

No gene information for fer-15

Entrez ID
Symbol
GenAge
Wormbase ID

3565745
shc-1
View on GenAge (shc-1)
WBGene00018788

SHC-transforming protein homolog 1

Locus: CELE_F54A5.3

Wormbase description: shc-1 encodes four proteins by multiple splicing, three of which are rather small (52-81 residues); however, one isoform (F54A5.3A, 316 residues) is a ortholog of vertebrate Shc proteins (e.g., p52/p46SHC and p66SHC); like its orthologs, F54A5.3A has a PTB and an SH2 domain in N- to C-terminal order; shc-1 interacts with both the JNK and insulin signaling pathways to regulate stress response and adult life span; SHC-1::GFP is widely expressed during postembryonic development and localizes to both the cytoplasm and the nucleus.

Orthologs of fer-15;shc-1 in SynergyAge

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Species	Gene

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Species	Gene

Orthologs of fer-15 in SynergyAge

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Species	Gene

Orthologs of shc-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Shc
Mus musculus	Shc1
Mus musculus	Shc3
Mus musculus	Shc4
Mus musculus	Shc2