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Description

Forkhead box protein K1 (UniProt: P85037, also known as Myocyte nuclear factor, MNF) is encoded by the FOXK1 (also known as MNF) gene (Gene ID: 221937) in human. Forkhead box protein K1 is a transcriptional regulator that binds to the upstream enhancer region (CCAC box) of myoglobin gene. It is an important regulatory factor of the myogenic progenitor cell population. It is involved in the cell cycle process and promotes proliferation by repressing Foxo4 transcriptional activity and the cyclin-dependent kinase inhibitor, p21CIP, in the myogenic progenitor cells. It is shown to represses myogenic differentiation by inhibiting MEFC activity and has a role in remodeling processes of adult muscles that occur in response to physiological stimuli. It is shown to be essential for correct temporal orchestration of molecular and cellular events necessary for muscle repair. Forkhead box protein K1 is expressed both developing and adult tissues. In adults, significant expression is seen in tumors of the brain, colon, and lymph node. Two isoforms of Forkhead box protein K1 have been reported that are produced by alternative splicing. Both FOXK1 and FOXK2 proteins are shown to act as transcriptional repressors of autophagy in muscle cells and fibroblasts. They specifically recruit Sin3A HDAC complexes to restrict acetylation of histone H4 and expression of critical autophagy genes. The loss of FOXK1 and FOXK2 proteins results in the upregulation of several genes controlling the initiation and nucleation of autophagosome formation. (Ref.: Bowman, CJ., et al. (2014). Nature Cell Biology 16(12), 1202-1214).