FOXO4

Forkhead box protein O4 ;
Fork head domain transcription factor AFX1 ;

disease:A chromosomal aberration involving FOXO4 is found in acute leukemias. Translocation t(X;11)(q13;q23) with MLL/HRX. The result is a rogue activator protein.,function:Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle.,pharmaceutical:A constitutively active FOXO4 mutant where phosphorylation sites Thr-32, Ser-187 and Ser-262 have been mutated to alanine may have therapeutic potential in ERBB2/HER2-overexpressing cancers as it inhibits ERBB2-mediated cell survival, transformation and tumorigenicity.,PTM:Acetylation by CBP, which is induced by peroxidase stress, inhibits transcriptional activity. Deacetylation by SIRT1 is NAD-dependent and stimulates transcriptional activity.,PTM:Phosphorylation by PKB/AKT1 inhibits transcriptional activity and is responsible for cytoplasmic localization.,similarity:Contains 1 fork-head DNA-binding domain.,subcellular location:When phosphorylated, translocated from nucleus to cytoplasm. Dephosphorylation triggers nuclear translocation.,subunit:Interacts with CBP, MYOCD, SIRT1, SRF and YWHAZ. Acetylated by CBP and deacetylated by SIRT1. Binding of YWHAZ inhibits DNA-binding.,tissue specificity:Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform zeta is most abundant in the liver, kidney, and pancreas.,

cell cycle checkpoint, DNA damage checkpoint, G1 phase of mitotic cell cycle, mitotic cell cycle, transcription,transcription, DNA-dependent, regulation of transcription, DNA-dependent, transcription from RNA polymerase II promoter, response to DNA damage stimulus, cell cycle, cell cycle arrest, mitotic cell cycle checkpoint, mitotic cell cycle G2/M transition DNA damage checkpoint, cell surface receptor linked signal transduction, enzyme linked receptor protein signaling pathway, transmembrane receptor protein tyrosine kinase signaling pathway, intracellular signaling cascade, regulation of mitotic cell cycle, muscle organ development, negative regulation of cell proliferation, 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, negative regulation of angiogenesis, cell cycle process, cell cycle phase, positive regulation of cellular biosynthetic process, DNA integrity checkpoint, G2/M transition DNA damage checkpoint, G2/M transition checkpoint, RNA biosynthetic process, response to insulin stimulus, cellular response to insulin stimulus, cellular response to hormone stimulus, cellular response to stress, regulation of cell proliferation, DNA damage response, signal transduction, response to peptide hormone stimulus, regulation of transcription, negative regulation of cell differentiation, regulation of angiogenesis, positive regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process, positive regulation of transcription, regulation of muscle cell differentiation, negative regulation of muscle cell differentiation, regulation of smooth muscle cell differentiation, negative regulation of smooth muscle cell differentiation, positive regulation of nitrogen compound metabolic process, regulation of RNA metabolic process, G1 phase, interphase, interphase of mitotic cell cycle, regulation of cell cycle,

Cytoplasm. Nucleus. When phosphorylated, translocated from nucleus to cytoplasm. Dephosphorylation triggers nuclear translocation. Monoubiquitination increases nuclear localization. When deubiquitinated, translocated from nucleus to cytoplasm.

Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform zeta is most abundant in the liver, kidney, and pancreas.