FOXK1 and its closely relate sibling FOXK2 induce aerobic glycolysis by upregulating the enzymatic machinery required for this (for example, hexokinase-2, phosphofructokinase, pyruvate kinase, and lactate dehydrogenase), while at the same time suppressing further oxidation of pyruvate in the mitochondria by increasing the activity of pyruvate dehydrogenase kinases 1 and 4. Together with suppression of the catalytic subunit of pyruvate dehydrogenase phosphatase 1 this leads to increased phosphorylation of the E1α regulatory subunit of the pyruvate dehydrogenase complex, which in turn inhibits further oxidation of pyruvate in the mitochondria—instead, pyruvate is reduced to lactate. Suppression of FOXK1 and FOXK2 induce the opposite phenotype. Both in vitro and in vivo experiments, including studies of primary human cells, show how FOXK1 and/or FOXK2 are likely to act as important regulators that reprogram cellular metabolism to induce aerobic glycolysis.[7]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Katoh M, Katoh M (July 2004). "Identification and characterization of human FOXK1 gene in silico". International Journal of Molecular Medicine. 14 (1): 127–132. doi:10.3892/ijmm.14.1.127. PMID15202027.
Huang JT, Lee V (September 2004). "Identification and characterization of a novel human FOXK1 gene in silico". International Journal of Oncology. 25 (3): 751–757. doi:10.3892/ijo.25.3.751. PMID15289879.
PDB gallery
2a3s: Solution structure and Dynamics of DNA-Binding Domain of Myocyte Nuclear Factor
2d2w: Solution structure and Dynamics of the DNA-Binding Domain of Myocyte Nuclear Factor
