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 (Jun 2004). "Identification and characterization of human FOXK1 gene in silico". Int J Mol Med. 14 (1): 127–32.
doi:
10.3892/ijmm.14.1.127.
PMID15202027.
Huang JT, Lee V (2005). "Identification and characterization of a novel human FOXK1 gene in silico". Int. J. Oncol. 25 (3): 751–7.
doi:
10.3892/ijo.25.3.751.
PMID15289879.