Phospho-FOXO3a (S253) Recombinant Rabbit Monoclonal Antibody [ST49-01] (ET1609-49)

UNIPROT #

O43524

PROTEIN NAME

Phospho-FOXO3a (S253)

SYNONYMS

AF6q21 antibody;AF6q21 protein antibody;DKFZp781A0677 antibody;FKHR2 antibody;FKHRL 1 antibody;FKHRL1 antibody;FKHRL1P2 antibody;Forkhead (Drosophila) homolog (rhabdomyosarcoma) like 1 antibody;Forkhead box O3 antibody;Forkhead box O3A antibody;Forkhead box protein O3 antibody;Forkhead box protein O3A antibody;Forkhead Drosophila homolog of in rhabdomyosarcoma like 1 antibody;Forkhead homolog (rhabdomyosarcoma) like 1 antibody;Forkhead in rhabdomyosarcoma like 1 antibody;Forkhead in rhabdomyosarcoma-like 1 antibody;FOX O3A antibody;FOXO2 antibody;foxo3 antibody;FOXO3_HUMAN antibody;FOXO3A antibody;MGC12739 antibody;MGC31925 antibody

TISSUE SPECIFICITY

Ubiquitous.

POST-TRANSLATIONAL MODIFICATION

In the presence of survival factors such as IGF-1, phosphorylated on Thr-32 and Ser-253 by AKT1/PKB. This 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. Although AKT1/PKB doesn't appear to phosphorylate Ser-315 directly, it may activate other kinases that trigger phosphorylation at this residue. Phosphorylated by STK4/MST1 on Ser-209 upon oxidative stress, which leads to dissociation from YWHAB/14-3-3-beta and nuclear translocation. Phosphorylated by PIM1. Phosphorylation by AMPK leads to the activation of transcriptional activity without affecting subcellular localization. In response to metabolic stress, phosphorylated by AMPK on Ser-30 which mediates FOXO3 mitochondrial translocation. Phosphorylation by MAPKAPK5 promotes nuclear localization and DNA-binding, leading to induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation. Phosphorylated by CHUK/IKKA and IKBKB/IKKB. TNF-induced inactivation of FOXO3 requires its phosphorylation at Ser-644 by IKBKB/IKKB which promotes FOXO3 retention in the cytoplasm, polyubiquitination and ubiquitin-mediated proteasomal degradation. May be dephosphorylated by calcineurin A on Ser-299 which abolishes FOXO3 transcriptional activity (By similarity). In cancer cells, ERK mediated-phosphorylation of Ser-12 is required for mitochondrial translocation of FOXO3 in response to metabolic stress or chemotherapeutic agents.; Deacetylation by SIRT1 or SIRT2 stimulates interaction of FOXO3 with SKP2 and facilitates SCF(SKP2)-mediated FOXO3 ubiquitination and proteasomal degradation. Deacetylation by SIRT2 stimulates FOXO3-mediated transcriptional activity in response to oxidative stress (By similarity). Deacetylated by SIRT3. Deacetylation by SIRT3 stimulates FOXO3-mediated mtDNA transcriptional activity in response to metabolic stress.; Heavily methylated by SET9 which decreases stability, while moderately increasing transcriptional activity. The main methylation site is Lys-271. Methylation doesn't affect subcellular location.; Polyubiquitinated. Ubiquitinated by a SCF complex containing SKP2, leading to proteasomal degradation.; The N-terminus is cleaved following import into the mitochondrion.

SUBCELLULAR LOCATION

Cytoplasm, Membrane, Mitochondrion, Mitochondrion outer membrane, Nucleus.

FUNCTION

FOXO3 belongs to the O subclass of the forkhead family of transcription factors which are characterized by a distinct fork head DNA-binding domain. There are three other FoxO family members in humans, FOXO1, FOXO4 and FOXO6. These transcription factors share the ability to be inhibited and translocated out of the nucleus on phosphorylation by proteins such as Akt/PKB in the PI3K signaling pathway (aside from FOXO6, which may be constitutively nuclear). Other post-translational modifications including acetylation and methylation are seen and can result in increased or altered FOXO3a activity. The use of FOXO3a knockout mice has revealed a diverse range of functions in both health and disease, namely infertility, lymphoproliferation, adenoma, organ inflammation, metabolism etc.; yet despite the purported importance of FOXO transcription factors in aging, FOXO3A knockout mice do not show an obvious shortening of lifespan or accelerated aging.