hcf-1;sgk-1

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Genetic mutants with hcf-1, sgk-1 alterations

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

Temperature °C
20
Diet
OP50
Lifespan (days)
22.0
Lifespan change (compared to wild type)
17.65%
Phenotype
In hcf-1(null) animals, sgk-1(gf) did not further increase lifespan
Lifespan comparisons
Double mutant hcf-1(pk924);sgk-1(ft15) has a lifespan of 22.0 days, while single mutant sgk-1(ft15) has a lifespan of 19.8 days, single mutant hcf-1(pk924) has a lifespan of 20.6 days and wild type has a lifespan of 18.7 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Chen AT et al., 2013, Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation. Aging Cell. 12(5):932-40 23786484 Click here to select all mutants from this PubMed ID in the graph
Abstract
The AGC family serine-threonine kinases Akt and Sgk are similar in primary amino acid sequence and in vitro substrate specificity, and both kinases are thought to directly phosphorylate and inhibit FoxO transcription factors. In the nematode Caenorhabditis elegans, it is well established that AKT-1 controls dauer arrest and lifespan by regulating the subcellular localization of the FoxO transcription factor DAF-16. SGK-1 is thought to act similarly to AKT-1 in lifespan control by phosphorylating and inhibiting the nuclear translocation of DAF-16/FoxO. Using sgk-1 null and gain-of-function mutants, we now provide multiple lines of evidence indicating that AKT-1 and SGK-1 influence C. elegans lifespan, stress resistance, and DAF-16/FoxO activity in fundamentally different ways. Whereas AKT-1 shortens lifespan, SGK-1 promotes longevity in a DAF-16-/FoxO-dependent manner. In contrast to AKT-1, which reduces resistance to multiple stresses, SGK-1 promotes resistance to oxidative stress and ultraviolet radiation but inhibits thermotolerance. Analysis of several DAF-16/FoxO target genes that are repressed by AKT-1 reveals that SGK-1 represses a subset of these genes while having little influence on the expression of others. Accordingly, unlike AKT-1, which promotes the cytoplasmic sequestration of DAF-16/FoxO, SGK-1 does not influence DAF-16/FoxO subcellular localization. Thus, in spite of their similar in vitro substrate specificities, Akt and Sgk influence longevity, stress resistance, and FoxO activity through distinct mechanisms in vivo. Our findings highlight the need for a re-evaluation of current paradigms of FoxO regulation by Sgk.

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

Temperature °C
20
Diet
OP50
Lifespan (days)
11.5
Lifespan change (compared to wild type)
-38.50%
Lifespan comparisons
Double mutant hcf-1(pk924);sgk-1(mg455) has a lifespan of 11.5 days, while single mutant hcf-1(pk924) has a lifespan of 20.6 days and wild type has a lifespan of 18.7 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Chen AT et al., 2013, Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation. Aging Cell. 12(5):932-40 23786484 Click here to select all mutants from this PubMed ID in the graph
Abstract
The AGC family serine-threonine kinases Akt and Sgk are similar in primary amino acid sequence and in vitro substrate specificity, and both kinases are thought to directly phosphorylate and inhibit FoxO transcription factors. In the nematode Caenorhabditis elegans, it is well established that AKT-1 controls dauer arrest and lifespan by regulating the subcellular localization of the FoxO transcription factor DAF-16. SGK-1 is thought to act similarly to AKT-1 in lifespan control by phosphorylating and inhibiting the nuclear translocation of DAF-16/FoxO. Using sgk-1 null and gain-of-function mutants, we now provide multiple lines of evidence indicating that AKT-1 and SGK-1 influence C. elegans lifespan, stress resistance, and DAF-16/FoxO activity in fundamentally different ways. Whereas AKT-1 shortens lifespan, SGK-1 promotes longevity in a DAF-16-/FoxO-dependent manner. In contrast to AKT-1, which reduces resistance to multiple stresses, SGK-1 promotes resistance to oxidative stress and ultraviolet radiation but inhibits thermotolerance. Analysis of several DAF-16/FoxO target genes that are repressed by AKT-1 reveals that SGK-1 represses a subset of these genes while having little influence on the expression of others. Accordingly, unlike AKT-1, which promotes the cytoplasmic sequestration of DAF-16/FoxO, SGK-1 does not influence DAF-16/FoxO subcellular localization. Thus, in spite of their similar in vitro substrate specificities, Akt and Sgk influence longevity, stress resistance, and FoxO activity through distinct mechanisms in vivo. Our findings highlight the need for a re-evaluation of current paradigms of FoxO regulation by Sgk.

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

Temperature °C
20
Diet
OP50
Lifespan (days)
11.2
Lifespan change (compared to wild type)
-40.11%
Lifespan comparisons
Double mutant hcf-1(pk924);sgk-1(ok538) has a lifespan of 11.2 days, while single mutant hcf-1(pk924) has a lifespan of 20.6 days and wild type has a lifespan of 18.7 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Chen AT et al., 2013, Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation. Aging Cell. 12(5):932-40 23786484 Click here to select all mutants from this PubMed ID in the graph
Abstract
The AGC family serine-threonine kinases Akt and Sgk are similar in primary amino acid sequence and in vitro substrate specificity, and both kinases are thought to directly phosphorylate and inhibit FoxO transcription factors. In the nematode Caenorhabditis elegans, it is well established that AKT-1 controls dauer arrest and lifespan by regulating the subcellular localization of the FoxO transcription factor DAF-16. SGK-1 is thought to act similarly to AKT-1 in lifespan control by phosphorylating and inhibiting the nuclear translocation of DAF-16/FoxO. Using sgk-1 null and gain-of-function mutants, we now provide multiple lines of evidence indicating that AKT-1 and SGK-1 influence C. elegans lifespan, stress resistance, and DAF-16/FoxO activity in fundamentally different ways. Whereas AKT-1 shortens lifespan, SGK-1 promotes longevity in a DAF-16-/FoxO-dependent manner. In contrast to AKT-1, which reduces resistance to multiple stresses, SGK-1 promotes resistance to oxidative stress and ultraviolet radiation but inhibits thermotolerance. Analysis of several DAF-16/FoxO target genes that are repressed by AKT-1 reveals that SGK-1 represses a subset of these genes while having little influence on the expression of others. Accordingly, unlike AKT-1, which promotes the cytoplasmic sequestration of DAF-16/FoxO, SGK-1 does not influence DAF-16/FoxO subcellular localization. Thus, in spite of their similar in vitro substrate specificities, Akt and Sgk influence longevity, stress resistance, and FoxO activity through distinct mechanisms in vivo. Our findings highlight the need for a re-evaluation of current paradigms of FoxO regulation by Sgk.

Search genes: hcf-1 sgk-1

Entrez ID
Symbol
GenAge
Wormbase ID

177560
hcf-1
View on GenAge (hcf-1)
WBGene00001827

human HCF1 related

Locus: CELE_C46A5.9

Wormbase description: hcf-1 encodes the C. elegans ortholog of human host cell factor (HCF-1), a transcriptional regulator that associates with histone modification enzymes and plays a role in cell cycle progression; in C. elegans, hcf-1 plays a role in regulation of cell division and mitotic histone modification; in addition, HCF-1 functions in determination of adult lifespan as a negative regulator of DAF-16, with which it physically interacts; HCF-1 is a ubiquitously expressed protein that localizes to the nucleus.

Entrez ID
Symbol
GenAge
Wormbase ID

181697
sgk-1
View on GenAge (sgk-1)
WBGene00004789

Serine/threonine-protein kinase sgk-1

Locus: CELE_W10G6.2

Wormbase description: sgk-1 encodes a serine/threonine protein kinase that is orthologous to the mammalian serum- and glucocorticoid-inducible kinases (SGKs); in C. elegans, sgk-1 activity is required for normal egg laying, generation time, stress response, and adult life span; SGK-1 forms a complex with the AKT kinases with which it functions in parallel to mediate certain aspects of DAF-2/insulin-signaling; SGK-1 phosphorylates DAF-16 in vitro in a manner strictly dependent upon pdk-1 which encodes a 3-phosphoinositide-dependent kinase; an SGK-1::GFP fusion protein is expressed beginning in late embryonic stages and in larvae is seen in sensory and motor neurons as well as in the intestine; in neurons SGK-1::GFP localizes to the cytoplasm and the nucleus, while in the intestine SGK-1::GFP is found exclusively in the cytoplasm.

Orthologs of hcf-1;sgk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Hcfc1;Sgk3
Mus musculus	Hcfc1;Sgk2
Mus musculus	Hcfc1;Sgk1

Orthologs of hcf-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hcf
Mus musculus	Hcfc1

Orthologs of sgk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Sgk3
Mus musculus	Sgk2
Mus musculus	Sgk1