forkhead box protein O4; forkhead domain transcription factor AFX1 (FOXO4, AFX1)

Function

• transcription factor
• role in regulation of insulin signaling pathway
• binds to insulin-response elements (IREs) & can activate transcription of IGFBP1
• down-regulates expression of HIF1A & suppresses hypoxia- induced transcriptional activation of HIF1A-modulated genes
• role in negative regulation of the cell cycle
• interacts with CBP, MYOCD, SIRT1, SRF & YWHAZ
• acetylated by CBP & deacetylated by SIRT1
• binding of YWHAZ inhibits DNA-binding
• acetylation by CBP, which is induced by peroxidase stress, inhibits transcriptional activity
• deacetylation by SIRT1 is NAD-dependent & stimulates transcriptional activity
• phosphorylation by PKB/AKT1 inhibits transcriptional activity & is responsible for cytoplasmic localization

Compartment

• cytoplasm, nucleus
• when phosphorylated, translocated from nucleus to cytoplasm
• dephosphorylation triggers nuclear translocation

Alternative splicing

named isoforms=2

Expression

• expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney & pancreas
• isoform zeta is most abundant in liver, kidney, & pancreas

Pathology

-chromosomal translocation t(X;11)(q13;q23) involving FOXO4 with MLL/HRX is found in acute leukemias The result is a rogue activator protein

More general terms

• forkhead family transcription factor
• phosphoprotein

Database

• OMIM: https://mirror.omim.org/entry/300033
• UniProt: http://www.uniprot.org/uniprot/P98177.html