FOXO1

Forkhead box protein O1 ;
Forkhead box protein O1A ;
Forkhead in rhabdomyosarcoma ;

disease:Chromosomal aberrations involving FOXO1 are a cause of rhabdomyosarcoma 2 (RMS2) [MIM:268220]; also known as alveolar rhabdomyosarcoma. Translocation (2;13)(q35;q14) with PAX3; translocation t(1;13)(p36;q14) with PAX7. The resulting protein is a transcriptional activator.,function:Transcription factor.,PTM:Phosphorylated by AKT1; insulin-induced (By similarity). IGF1 rapidly induces phosphorylation of Ser-256, Thr-24, and Ser-319. Phosphorylation of Ser-256 decreases DNA-binding activity and promotes the phosphorylation of Thr-24, and Ser-319, permitting phosphorylation of Ser-322 and Ser-325, probably by CK1, leading to nuclear exclusion and loss of function. Phosphorylation of Ser-329 is independent of IGF1 and leads to reduced function. Phosphorylated upon DNA damage, probably by ATM or ATR.,similarity:Contains 1 fork-head DNA-binding domain.,subcellular location:Shuttles between cytoplasm and nucleus.,subunit:Interacts with LRPPRC.,tissue specificity:Ubiquitous.,

blood vessel development, vasculature development, transcription, regulation of transcription, DNA-dependent,regulation of transcription from RNA polymerase II promoter, anti-apoptosis, cell surface receptor linked signal transduction, enzyme linked receptor protein signaling pathway, transmembrane receptor protein tyrosine kinase signaling pathway, insulin receptor signaling pathway, response to endogenous stimulus, response to hormone stimulus, positive regulation of biosynthetic process, response to organic substance, positive regulation of macromolecule biosynthetic process, positive regulation of macromolecule metabolic process, positive regulation of gene expression, regulation of cell death, positive regulation of cellular biosynthetic process, response to insulin stimulus, cellular response to insulin stimulus, cellular response to hormone stimulus, regulation of cell proliferation,regulation of apoptosis, negative regulation of apoptosis, regulation of programmed cell death, negative regulation of programmed cell death, response to peptide hormone stimulus, regulation of transcription, positive regulation of transcription, DNA-dependent, positive regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process, positive regulation of transcription, positive regulation of transcription from RNA polymerase II promoter,positive regulation of nitrogen compound metabolic process, regulation of RNA metabolic process, positive regulation of RNA metabolic process, negative regulation of cell death,

Cytoplasm . Nucleus . Shuttles between the cytoplasm and nucleus. Largely nuclear in unstimulated cells (PubMed:11311120, PubMed:12228231, PubMed:19221179, PubMed:21245099, PubMed:20543840, PubMed:25009184). In osteoblasts, colocalizes with ATF4 and RUNX2 in the nucleus (By similarity). Serum deprivation increases localization to the nucleus, leading to activate expression of SOX9 and subsequent chondrogenesis (By similarity). Insulin-induced phosphorylation at Ser-256 by PKB/AKT1 leads, via stimulation of Thr-24 phosphorylation, to binding of 14-3-3 proteins and nuclear export to the cytoplasm where it is degraded by the ubiquitin-proteosomal pathway (PubMed:11237865, PubMed:12228231). Phosphorylation at Ser-249 by CDK1 disrupts binding of 14-3-3 proteins and promotes nuclear accumulation (PubMed:18356527). Phosphorylation by NLK results in nuclear export (By similarity). Translocates to the nucleus upon oxidative stress-induced phosphorylation at Ser-212 by STK4/MST1 (PubMed:19221179, PubMed:21245099). SGK1-mediated phosphorylation also results in nuclear translocation (By similarity). Retained in the nucleus under stress stimuli including oxidative stress, nutrient deprivation or nitric oxide (By similarity). Retained in the nucleus on methylation (By similarity). PPIA/CYPA stimulates its nuclear accumulation (PubMed:31063815). Deacetylation by SIRT6, promotes its translocation into the cytoplasm (PubMed:25009184). .

Ubiquitous.