Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C. Do not aliquot the antibody.
The Fox03a Antibody detects exogenous and endogenous levels of total Fox03a protein. The antibody does not detect the exogenously expressed family members Fox04 or Fox01. The antibody reacts with denatured components of bovine serum including BSA.
Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to the sequence of human Fox03a. Antibodies are purified by protein A and peptide affinity chromatography.
The Forkhead family of transcription factors is involved in tumorigenesis of rhabdomyosarcoma and acute leukemias (1-3). Within the family, three members (FoxO1, FoxO4, and FoxO3a) have sequence similarity to the nematode orthologue DAF-16, which mediates signaling via a pathway involving IGFR1, PI3K, and Akt (4-6). Active forkhead members act as tumor suppressors by promoting cell cycle arrest and apoptosis. Increased expression of any FoxO member results in the activation of the cell cycle inhibitor p27 Kip1. Forkhead transcription factors also play a part in TGF-β-mediated upregulation of p21 Cip1, a process negatively regulated through PI3K (7). Increased proliferation results when forkhead transcription factors are inactivated through phosphorylation by Akt at Thr24, Ser256, and Ser319, which results in nuclear export and inhibition of transcription factor activity (8). Forkhead transcription factors can also be inhibited by the deacetylase sirtuin (SirT1) (9).
In Fox03a, the three sites phosphorylated by Akt mentioned above are Thr32, Ser253 and Ser315. Fox03a associates with 14-3-3 proteins upon phosphorylation by Akt and is retained in the cytoplasm. In the absence of survival factors, Fox03a is dephosphorylated, translocates to the nucleus and triggers cell death by a Fas ligand-dependent mechanism (7).
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