fem-1;fer-15;xbp-1

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Genetic mutants with fem-1, fer-15, xbp-1 alterations

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

Lifespan (days)
13.7
Lifespan comparisons
Triple mutant fem-1(hc17);fer-15(b26);xbp-1(RNAi) has a lifespan of 13.7 days, while double mutant fem-1(hc17);fer-15(b26) has a lifespan of 17.2 days.
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Search genes: fem-1 fer-15 xbp-1 fem-1;fer-15;xbp-1

Entrez ID
Symbol
GenAge
Wormbase ID

177335
fem-1
View on GenAge (fem-1)
WBGene00001411

Sex-determining protein fem-1

Locus: CELE_F35D6.1

Wormbase description: The fem-1 gene encodes an ankyrin repeat-containing protein orthologous to human FEM1A and is required for masculinization of germline and somatic tissues; FEM-1 is widely expressed and functions as a second messenger in the sex determination pathway, connecting the membrane protein TRA-2A to the transcription factor TRA-1A which it negatively regulates; FEM-1 may also play a role in apoptosis, as it is a substrate for the CED-3 protease and can induce apoptosis when overexpressed in mammalian cells.

Symbol
GenAge

fer-15
View on GenAge (fer-15)

No gene information for fer-15

Entrez ID
Symbol
GenAge
Wormbase ID

175541
xbp-1
View on GenAge (xbp-1)
WBGene00006959

X-box Binding Protein homolog

Locus: CELE_R74.3

Wormbase description: xbp-1 encodes a bZIP transcription factor orthologous to yeast Hac1 and mammalian X box-binding protein 1 (XBP-1, OMIM:194355); XBP-1 is required for the unfolded protein response (UPR) that counteracts cellular stress induced by accumulation of unfolded proteins in the endoplasmic reticulum (ER); xbp-1 mRNA is spliced by the IRE-1 endoribonuclease to promote translation of transcriptionally active XBP-1 that positively regulates UPR gene expression to maintain ER homeostasis and promote normal development; loss of xbp-1 activity also results in near-complete loss of myo-2 pharnygeal myosin expression, although pharyngeal muscle is still present.

Orthologs of fem-1;fer-15;xbp-1 in SynergyAge

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Orthologs of fem-1 in SynergyAge

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Orthologs of fer-15 in SynergyAge

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Orthologs of xbp-1 in SynergyAge

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SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.