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) . .