FOXK1

Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis, muscle cell differentiation and autophagy (PubMed:25402684, PubMed:29861159, PubMed:30700909). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:25402684, PubMed:29861159, PubMed:30700909). Together with FOXK2, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (PubMed:30700909). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (PubMed:30700909). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (PubMed:30700909). Involved in mTORC1-mediated metabolic reprogramming: in response to mTORC1 signaling, translocates into the nucleus and regulates the expression of genes associated with glycolysis and downstream anabolic pathways, such as HIF1A, thereby regulating glucose metabolism (PubMed:29861159). Together with FOXK2, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (PubMed:25402684). Acts as a transcriptional regulator of the myogenic progenitor cell population in skeletal muscle (PubMed:8007964, PubMed:9271401, PubMed:12446708, PubMed:22956541). Binds to the upstream enhancer region (CCAC box) of myoglobin (MB) gene, regulating the myogenic progenitor cell population (PubMed:8007964, PubMed:9271401). Promotes muscle progenitor cell proliferation by repressing the transcriptional activity of FOXO4, thereby inhibiting myogenic differentiation (PubMed:12446708, PubMed:22956541). Involved in remodeling processes of adult muscles that occur in response to physiological stimuli (PubMed:9271401, PubMed:22956541). Required to correct temporal orchestration of molecular and cellular events necessary for muscle repair (PubMed:10792059). Represses myogenic differentiation by inhibiting MEFC activity (PubMed:22956541). Positively regulates Wnt/beta-catenin signaling by translocating DVL into the nucleus (By similarity). Reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression (By similarity). {ECO:0000250|UniProtKB:P85037, ECO:0000269|PubMed:10792059, ECO:0000269|PubMed:12446708, ECO:0000269|PubMed:22956541, ECO:0000269|PubMed:25402684, ECO:0000269|PubMed:29861159, ECO:0000269|PubMed:30700909, ECO:0000269|PubMed:8007964, ECO:0000269|PubMed:9271401}.(Source UnitProtKB).

forkhead box K1

Source UniprotKB

Mus musculus [tax_id: 10090]

mm10