Anti-phospho-FKHRL1/FOXO3A (Thr32) from rabbit, purified by affinity chromatography

Forkhead box protein O3 (UniProt: O43524; also known as AF6q21 protein, Forkhead in rhabdomyosarcoma-like 1) is encoded by the FOXO3 (also known as FKHRL1, FOXO3A) gene (Gene ID: 2309) in human. Forkhead box protein O3 is a transcriptional activator that riggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. It recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. Its DNA binding domain located in amino acids 157-251. The nuclear localization signal is located in amino acids 242-259. In the cytoplasm it is present in an inactive state and it translocates to the nucleus upon oxidative stress and in the absence of survival factors. In the presence of survival factors such as IGF-1, it is phosphorylated on Thr32 and Ser253 by AKT1/PKB. The phosphorylated form then interacts with 14-3-3 proteins and is retained in the cytoplasm. Survival factor withdrawal induces dephosphorylation and promotes translocation to the nucleus where the dephosphorylated protein induces transcription of target genes and triggers apoptosis. Forkhead box protein O3 deacetylation by SIRT1 or SIRT2 stimulates its interaction SKP2 and facilitates SCF(SKP2)-mediated FOXO3 ubiquitination and proteasomal degradation. A chromosomal aberration involving FOXO3 is found in secondary acute leukemias.