Forkhead box (Fox) proteins are a family of evolutionarily conserved transcription factors containing a sequence known as Forkhead box or winged helix DNA binding domain. The human genome contains 43 Fox proteins that are divided into subfamilies. The FoxP subfamily has four members, FoxP1 - FoxP4, which are broadly expressed and play important roles in organ development, immune response and cancer pathogenesis. The FoxP subfamily has several characteristics that are atypical among Fox proteins: their Forkhead domain is located at the carboxy-terminal region and they contain motifs that promote homo- and heterodimerization. FoxP proteins usually function as transcriptional repressors.
FoxP1 plays an important role in cardiac valve and B cell development. Targeted deletion of FoxP1 in mice results in embryonic death at E14.5 with severe defects in cardiac outflow development, endocardial cushion morphogenesis, and myocyte proliferation and maturation. The FoxP1 gene is located on chromosome 3p14.1 and loss of heterozygosity of this region in multiple cancer types suggests a role for FoxP1 as a tumor suppressor. Alternatively, FoxP1 may also act as an oncogene as it is highly expressed in a variety of B cell malignancies and is frequently involved in chromosome translocation.
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