FKHR (for forkhead in rhabdomyosarcoma), FKHRL1, and AFX1 are members of a subfamily of the forkhead family of transcription factors. AFX1, also known as FoxO4, is expressed in a wide variety of tissues and, like other FKHR proteins, AFX1 contains a single forkhead domain and serine-proline-rich region, which mediate DNA binding. AFX1-mediated transcriptional activation is regulated by the serine/threonine kinase Akt1, which phosphorylates AFX1 and in turn, sequesters AFX1 in the cytosol, thereby blocking nuclear localization and DNA binding. Genetic mutations in FKHR genes, including the t(2;13) and t(1;3) translocations, are commonly found in alveolar rhabdomyosarcomas. Additionally, the t(x;11) translocation of the AFX1 gene, which involves the fusion of a serine-proline-rich sequence of AFX1 to the carboxy terminus of a truncated MLL, results in acute lymphocytic leukemia.
