Forkhead box proteins are a family of evolutionarily conserved transcription factors defined by the presence of a winged helix DNA-binding domain called a Forkhead box. In humans, there are over 40 known Fox protein family members, divided into 19 subfamilies, which have evolved to regulate gene transcription in diverse and highly specialized biological contexts throughout development. Mutations that disrupt the expression of Fox gene family members have consequently been implicated in a broad array of human disorders, including immunological dysfunction, infertility, speech/language disorders, and cancer.FoxK1 belongs to a subfamily of Fox proteins along with FoxK2. FoxK1 functions as a transcriptional repressor of downstream target genes, including FoxO4, Mef2, p21, PPGB, and ACTA2. There are two isoforms of FoxK1: FoxK1-α and FoxK1-β. The β isoform has a truncated C terminus compared to the α isoform. The two isoforms of FoxK1 show reciprocal expression patterns during muscle regeneration. FoxK1-β is expressed mainly in quiescent satellite cells, whereas FoxK1-α is the dominant isoform in proliferating myoblasts from activated satellite cells. Both isoforms of FoxK1 jointly regulate proliferation and differentiation of myogenic stem cells during development and muscle regeneration.
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