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Originally the product of the Drosophila homeobox gene fork head, a transcription factor. Subsequently many related transcription factors have been identified, and are now reclassified as forkhead box proteins (Fox proteins) with subclasses ranging from FoxA to FoxS. All are winged-helix transcription factors containing the forkhead box motif that binds DNA, and are involved in cell growth, proliferation, differentiation, longevity and embryonic development. The forkhead activin signal transducer (FAST, FoxH1, 365 aa) is expressed in most human tissues including breast, colon, thymus, and muscle, and in several cancer cell lines. It binds to SMAD2 and activates an activin response element. Forkhead homologue in rhabdomyosarcoma (FKHR, forkhead receptor, FoxO1, 655 aa) is translocated and fused with PAX3 or PAX7 in alveolar rhabdomyosarcomas. Activation in many cells induces cell cycle arrest followed by apoptosis but this is blocked when FKHR is phosphorylated by protein kinase B (Akt) which causes it to be transported to the cytoplasm. FKHR can interact with both steroid and nonsteroid nuclear receptors and, depending on the receptor, can act as either a coactivator or corepressor. Forkhead transcription factor in rhabdomyosarcoma like-1 ( FKHRL1, 673 aa) is related to FKHR and has a role in the regulation of the proliferation of vascular smooth muscle. See Fox.

Subjects: Medicine and Health.

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