GenAge Human Genes Help Human Ageing Genomic Resources Citation

GenAge entry for FOXO1 (Homo sapiens)


Gene name (HAGRID: 0124)

HGNC symbolFOXO1
AliasesFKHR; FOXO1A; FKH1
Common nameforkhead box O1

Potential relevance to the human ageing process

Main reason for selection

Entry selected based on evidence directly linking the gene product to ageing in a non-mammalian animal model

Description

A transcription factor of the Fox family, FOXO1 is important in development [0802]. It also appears to regulate apoptotic signals.

A homologue of FOXO1A, daf-16, has been associated with ageing in roundworms [0628], and overexpression of another homologue, dFOXO, in adult fat body of fruit flies increased longevity in females [1238]. Mice overexpressing FOXO1 in skeletal muscle weighed less than controls and had a reduced skeletal muscle mass, suggesting that FOXO1 could play a role in the age-related decline in muscle mass [1467]. Results from mice also suggest that FOXO1 could be involved in type 2 diabetes [0630]. Although at present there is no evidence directly linking FOXO1 to human ageing, it remains a putative player in the human ageing process.

Cytogenetic information

Cytogenetic band13q14.1
Location40,027,816 bp to 40,138,734 bp
OrientationMinus strand
Display region using the UCSC Genome Browser

Protein information

Functionapoptosis, growth and development
Cellular locationnucleus, cytoplasm
Expressionpre natal, CNS, immune system, germ cells, stem cells, other
Gene Ontology

GO:0001568; blood vessel development; Process
GO:0006350; transcription; Process
GO:0006355; regulation of transcription, DNA-dependent; Process
GO:0008286; insulin receptor signaling pathway; Process
GO:0042127; regulation of cell proliferation; Process

GO:0003700; transcription factor activity; Function

Protein-protein interactions

Interacting proteinsCREBBP, CEBPB, AR, YWHAZ, ESR1.
Display interactions using the IGD

Retrieve sequences for FOXO1

ORFORF
CDSCDS

Homologues in model organisms

P. troglodytesFOXO1 (forkhead box O1)
C. lupus familiarisFOXO1 (forkhead box O1)
M. musculusFoxo1 (forkhead box O1)
R. norvegicusFoxo1a (forkhead box O1A)
G. gallusFOXO1A (forkhead box O1A)
D. reriofoxo1a.2 (fox family transcription factor FoxO1a.2)
HomoloGene (1527)

Selected references

[1909] de Candia et al. (2008), A combination of genomic approaches reveals the role of FOXO1a in regulating an oxidative stress response pathway, PubMed
[1930] Alcendor et al. (2007), Sirt1 regulates aging and resistance to oxidative stress in the heart, PubMed
[1937] Tothova et al. (2007), FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress, PubMed
[1775] Baugh and Sternberg (2006), DAF-16/FOXO regulates transcription of cki-1/Cip/Kip and repression of lin-4 during C. elegans L1 arrest, PubMed
[1771] Fukuyama et al. (2006), C. elegans DAF-18/PTEN mediates nutrient-dependent arrest of cell cycle and growth in the germline, PubMed
[1583] Greer and Brunet (2005), FOXO transcription factors at the interface between longevity and tumor suppression, PubMed
[1514] Yamamoto et al. (2005), Regulation of oxidative stress by the anti-aging hormone Klotho, PubMed
[1541] McColl et al. (2005), The C. elegans ortholog of mammalian Ku70, interacts with insulin-like signaling to modulate stress resistance and life span, PubMed
[1358] Essers et al. (2005), Functional interaction between beta-catenin and FOXO in oxidative stress signaling, PubMed
[1334] Papaconstantinou et al. (2005), Hepatic gene and protein expression of primary components of the IGF-I axis in long lived Snell dwarf mice, PubMed
[0060] Oh et al. (2005), JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16, PubMed
[1256] Kojima et al. (2004), Association analysis between longevity in the Japanese population and polymorphic variants of genes involved in insulin and insulin-like growth factor 1 signaling pathways, PubMed
[1743] Altomonte et al. (2004), Foxo1 mediates insulin action on apoC-III and triglyceride metabolism, PubMed
[1107] Quarrie and Riabowol (2004), Murine models of life span extension, PubMed
[1467] Kamei et al. (2004), Skeletal muscle FOXO1 (FKHR) transgenic mice have less skeletal muscle mass, down-regulated type I (slow twitch/red muscle) fiber genes, and impaired glycemic control, PubMed
[1095] Daitoku et al. (2004), Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity, PubMed
[1238] Giannakou et al. (2004), Long-lived Drosophila with overexpressed dFOXO in adult fat body, PubMed
[1153] Antebi (2004), Inside insulin signaling, communication is key to long life, PubMed
[1146] Maier et al. (2004), Modulation of mammalian life span by the short isoform of p53, PubMed
[1015] Coffer (2003), OutFOXing the grim reaper: novel mechanisms regulating longevity by forkhead transcription factors, PubMed
[0309] Purdom and Chen (2003), Linking oxidative stress and genetics of aging with p66Shc signaling and forkhead transcription factors, PubMed
[0314] McElwee et al. (2003), Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16, PubMed
[0315] Murphy et al. (2003), Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans, PubMed
[0141] Bonafe et al. (2003), Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control, PubMed
[0802] Lehmann et al. (2003), Fox's in development and disease, PubMed
[0371] Purdom and Chen (2003), p66(Shc): at the crossroad of oxidative stress and the genetics of aging, PubMed
[0626] Hsu et al. (2003), Regulation of aging and age-related disease by DAF-16 and heat-shock factor, PubMed
[1469] Nakae et al. (2003), The forkhead transcription factor Foxo1 regulates adipocyte differentiation, PubMed
[0801] Furuyama et al. (2002), Effects of aging and caloric restriction on the gene expression of Foxo1, 3, and 4 (FKHR, FKHRL1, and AFX) in the rat skeletal muscles, PubMed
[0630] Nakae et al. (2002), Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1, PubMed
[0629] Alvarez et al. (2001), Forkhead transcription factors contribute to execution of the mitotic programme in mammals, PubMed
[0326] Lin et al. (2001), Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling, PubMed
[0199] Tissenbaum and Guarente (2001), Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans, PubMed
[1468] Anderson et al. (2001), Embryonic expression of the tumor-associated PAX3-FKHR fusion protein interferes with the developmental functions of Pax3, PubMed
[0972] Medema et al. (2000), AFX-like forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27(kip1), PubMed
[0958] Honda and Honda (1999), The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans, PubMed
[1820] Lakowski and Hekimi (1998), The genetics of caloric restriction in Caenorhabditis elegans, PubMed
[0957] Lin et al. (1997), daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans, PubMed
[0628] Ogg et al. (1997), The fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans, PubMed

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External links

EPD
ORF AccessionNM_002015
CDS AccessionNP_002006
OMIM136533
HPRD00645
EnsemblFOXO1
UniProt/Swiss-ProtFOXO1_HUMAN
GeneCardsFOXO1
Entrez Gene2308
UniGene370666
GenAtlasFOXO1
InternetSearch Google


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