FOXO3
FOXO3 (Forkhead box protein O3) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Breast cancer, Skin cancer, Acute myeloid leukaemia and 1 more.
Overview
Transcriptional activator that recognises and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy. Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins. Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress.
Open Targets scores its association with cancer at 0.65 (direct and indirect evidence; datatypes literature 1.00, animal model 0.41, genetic association 0.05, somatic mutation 0.77). IntOGen calls it a driver in 2 cohorts (2 activating, 0 loss-of-function), covering Acute Myeloid Leukaemia, Medulloblastoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · FOXO3 (Forkhead box protein O3) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Breast cancer, Skin cancer, Acute myeloid leukaemia and 1 more.
- 1 · What it is
FOXO3 (Forkhead box protein O3) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Breast cancer, Skin cancer, Acute myeloid leukaemia and 1 more.
- 2 · What goes wrong in cancer
Transcriptional activator that recognises and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy.
- 3 · How drugs use it
No product in this corpus aims at FOXO3 yet. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
External identifiers
Sources: HGNC HGNC:3821 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt O43524 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000118689 (association with cancer (MONDO_0004992) 0.65; per-cancer scores at or above 0.5: skin cancer 0.52, breast cancer 0.54 (GraphQL API, CC0)); IntOGen FOXO3 (driver in 2 cohorts (Act 2, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Transcriptional activator that recognises and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy. Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins. Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation. In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription. In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription. Location: Cytoplasm, cytosol; Nucleus; Mitochondrion matrix; Mitochondrion outer membrane (UniProt). Locus 6q21 (HGNC).
- Breast cancer: Open Targets association 0.54 with breast cancer (MONDO_0007254)
- Skin cancer: Open Targets association 0.52 with skin cancer (MONDO_0002898)
- Acute myeloid leukaemia: IntOGen driver in 1 cohort (AML)
- Medulloblastoma: IntOGen driver in 1 cohort (MBL)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 2 cohorts; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"FOXO3" OR ABSTRACT:"FOXO3" OR TITLE:"forkhead box O3" OR ABSTRACT:"forkhead box O3" OR TITLE:"Forkhead box protein O3" OR ABSTRACT:"Forkhead box protein O3" OR TITLE:"AF6q21" OR ABSTRACT:"AF6q21" OR TITLE:"FOXO2" OR ABSTRACT:"FOXO2" OR TITLE:"FKHRL1" OR ABSTRACT:"FKHRL1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about FOXO3, not a curated reading list.
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