c-Fos Antibody

The Fos family of nuclear oncogenes includes c-Fos, FosB, Fos-related antigen 1 (FRA1), and Fos-related antigen 2 (FRA2) (1). While most Fos proteins exist as a single isoform, the FosB protein exists as two isoforms: full-length FosB and a shorter form, FosB2 (Delta FosB), which lacks the carboxy-terminal 101 amino acids (1-3). The expression of Fos proteins is rapidly and transiently induced by a variety of extracellular stimuli, including growth factors, cytokines, neurotransmitters, polypeptide hormones, and stress. Fos proteins dimerize with Jun proteins (c-Jun, JunB, and JunD) to form Activator Protein-1 (AP-1), a transcription factor that binds to TRE/AP-1 elements and activates transcription. Fos and Jun proteins contain the leucine-zipper motif that mediates dimerization and an adjacent basic domain that binds to DNA. The various Fos/Jun heterodimers differ in their ability to transactivate AP-1 dependent genes. In addition to increased expression, phosphorylation of Fos proteins by Erk kinases in response to extracellular stimuli may further increase transcriptional activity (4-6). Phosphorylation of c-Fos at Ser32 and Thr232 by Erk5 increases protein stability and nuclear localization (5). Phosphorylation of FRA1 at Ser252 and Ser265 by Erk1/2 increases protein stability and leads to overexpression of FRA1 in cancer cells (6). Following growth factor stimulation, expression of FosB and c-Fos in quiescent fibroblasts is immediate, but very short-lived, with protein levels dissipating after several hours (7). FRA1 and FRA2 expression persists longer, and appreciable levels can be detected in asynchronously growing cells (8). Deregulated expression of c-Fos, FosB, or FRA2 can result in neoplastic cellular transformation; however, Delta FosB lacks the ability to transform cells (2,3). 1.Tulchinsky, E. (2000) Histol Histopathol 15, 921-8. 2.Dobrazanski, P. et al. (1991) Mol Cell Biol 11, 5470-8. 3.Nakabeppu, Y. and Nathans, D. (1991) Cell 64, 751-9. 4.Rosenberger, S.F. et al. (1999) J Biol Chem 274, 1124-30. 5.Sasaki, T. et al. (2006) Mol Cell 24, 63-75. 6.Basbous, J. et al. (2007) Mol Cell Biol 27, 3936-50. 7.Kovary, K. and Bravo, R. (1991) Mol Cell Biol 11, 2451-9. 8.Kovary, K. and Bravo, R. (1992) Mol Cell Biol 12, 5015-23.