The mammalian forkhead O class transcription factors (FOXO) regulate diverse cellular processes such as metabolism, cell cycle, and apoptosis. Activity of these transcription factors can be regulated by diverse post-translational modifications including phosphorylation, acetylation, and ubiquitination (1). These modifications can alter nuclear transport, DNA binding, and protein-protein interactions to alter transcriptional activity. The best studied member of the FOXO family is FOXO1. FOXO transcription factors are expressed in nearly all tissues while FOXO1 is primarily expressed in insulin-responsive tissues (1). This expression pattern is important for FOXO1 regulation of gluconeogenesis and lipid metabolism. Downstream of the insulin/PI3K pathway FOXO1 is phosphorylated and inactivated by the serine-threonine kinase Akt (1). On the other hand FOXO1 activity enhanced following phosphorylation by JNK and subsequent nuclear localization (1). FOXO1 signaling in the regulation of diverse cellular processes makes it an important area of study in diabetes, carcinogenesis, inflammation and immunity, as well as wound healing (1). Research of FOXO1 and its isoforms will guide our knowledge of these clinically relevant areas of study.
FOXO1a antibodies serve as excellent tools to examine the nuclear to cytoplasmic transport by immunohistochemistry in response to changing cellular conditions or to examine phosphorylation status through western blotting. A study from the University of Dundee identified FOXO1a regulation as a primary mechanism of the experimental drug clioquinol in treating neurodegeneration (2). Using FOXO1a antibody, the researchers examined the effect of clioquinol on insulin signaling (2). Their study showed clioquinol triggers export of FOXO1a from the nucleus and, using phospho-specific FOXO1a antibodies, the researchers were able to identify the sites of post-translational modification responsive to drug treatment (2). Altering FOXO1a levels or activity can also be used to design strategies for the treatment of breast cancer. A study by Wu et al. used FOXO1a antibodies to examine protein levels in breast cancer cell lines that overexpress HER2 (3). They found HER2 overexpression leads to inactivation of FOXO1a and can lead to drug resistance (3). Western blotting with phospho-specific FOXO1a antibody showed HER2 enhances Akt signaling and leads to the inactivation of FOXO1a (3). By blocking Akt, the authors were able to restore FOXO1a expression and restore sensitivity to drug treatment (3). Further investigation of mechanisms of FOXO1a regulation is important for understanding the diverse cell signaling pathways FOXO1a functions.
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