FOXO1
Description
The FOXO1 (forkhead box O1) is a protein-coding gene located on chromosome 13.
Forkhead box protein O1 (FOXO1), also known as forkhead in rhabdomyosarcoma (FKHR), is a protein that in humans is encoded by the FOXO1 gene. FOXO1 is a transcription factor that plays important roles in regulation of gluconeogenesis and glycogenolysis by insulin signaling, and is also central to the decision for a preadipocyte to commit to adipogenesis. It is primarily regulated through phosphorylation on multiple residues; its transcriptional activity is dependent on its phosphorylation state.
== Function ==
=== Adipogenesis ===
FOXO1 negatively regulates adipogenesis. Presently, the exact mechanism by which this is accomplished is not entirely understood. In the currently accepted model, FOXO1 negatively regulates adipogenesis by binding to the promoter sites of PPARG and preventing its transcription. Rising levels of PPARG are required to initiate adipogenesis; by preventing its transcription, FOXO1 is preventing the onset of adipogenesis. During stimulation by insulin, FOXO1 is excluded from the nucleus and is subsequently unable to prevent transcription of PPARG and inhibit adipogenesis. However, there is substantial evidence to suggest that there are other factors that mediate the interaction between FOXO1 and the PPARG promoter, and that inhibition of adipogenesis is not entirely dependent on FOXO1 preventing transcription of PPARG. The failure to commit to adipogenesis is primarily due to active FOXO1 arresting the cell in G0/G1 through activation of yet unknown downstream targets, with a putative target being SOD2. FOXO1 belongs to the forkhead family of transcription factors that are characterized by a distinct fork head domain.
FOXO1 is a transcription factor that plays a crucial role in regulating metabolic homeostasis in response to oxidative stress. It binds to the insulin response element (IRE) and the Daf-16 family binding element (DBE) and is suppressed by insulin. FOXO1 acts as a key regulator of bone mass, chondrogenic commitment, glucose sensing in pancreatic beta cells, and gluconeogenesis in hepatocytes. It is also a significant regulator of cell death, promoting neural cell death and acting downstream of CDK1, PKB/AKT1, and STK4/MST1. FOXO1 mediates insulin action on adipose tissue, regulates the expression of adipogenic genes, and is involved in autophagy and apoptosis in various cell types. It interacts with numerous proteins, including LRPPRC, RUNX2, PPP2R1A, PPARG, XBP1, NLK, SIRT1, CDK1, YWHAG, YWHAZ, SKP2, KRIT1, ATF4, PRMT1, EP300, CREBBP, SIRT2, ATG7, CEBPA, WDFY2, CRY1, PPIA/CYPA, and TOX4, influencing its function and regulation.
FOXO1 is also known as FKH1, FKHR, FOXO1A.
