FOXK1

FOXK1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2A3S, 2D2W
Identifiers
Aliases	FOXK1 , FOXK1L, forkhead box K1
External IDs	OMIM: 616302 MGI: 1347488 HomoloGene: 82414 GeneCards: FOXK1
Gene location (Human)
Chr.	Chromosome 7 (human)
End	4,771,442 bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	142,462,011 bp
RNA expression pattern
	; ;
	More reference expression data
Gene ontology
Molecular function	• GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity ; • DNA binding ; • sequence-specific DNA binding ; • RNA polymerase II transcription regulatory region sequence-specific DNA binding ; • GO:0001948 protein binding ; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific ; • GO:0000975 transcription cis-regulatory region binding ; • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific ; • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific ;
Cellular component	• nucleus ; • nucleoplasm ; • cytoplasm ;
Biological process	• regulation of transcription by RNA polymerase II ; • positive regulation of transcription, DNA-templated ; • multicellular organism development ; • muscle organ development ; • negative regulation of transcription, DNA-templated ; • regulation of transcription, DNA-templated ; • transcription, DNA-templated ; • protein deubiquitination ; • anatomical structure morphogenesis ; • cell differentiation ; • negative regulation of transcription by RNA polymerase II ; • positive regulation of transcription by RNA polymerase II ;
	Sources:Amigo / QuickGO
Orthologs
	221937
	17425
	ENSG00000164916
	ENSMUSG00000056493
	P85037
	P42128
	NM_001037165
	NM_010812 ; NM_199068
	NP_001032242
	NP_951031
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated July 07, 2021

Forkhead box protein K1 is a transcription factor of the forkhead box family that in humans is encoded by the FOXK1 gene.^[5]^[6]

During starvation, in type 2 diabetes, in rapidly dividing cells during embryogenesis, in tumors (Warburg effect) and during T cell proliferation, aerobic glycolysis is induced to produce the building block to sustain growth. FOXK1 is one of the transcription factors managing the passage from the normal cellular respiration (complete glucose oxidation) to generating ATP and intermediaries for many other biochemical pathways.^[7]

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]

Related Research Articles

Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. Hypoxic microenvironements in solid tumors are a result of available oxygen being consumed within 70 to 150 μm of tumour vasculature by rapidly proliferating tumor cells thus limiting the amount of oxygen available to diffuse further into the tumor tissue. In order to support continuous growth and proliferation in challenging hypoxic environments, cancer cells are found to alter their metabolism. Furthermore, hypoxia is known to change cell behavior and is associated with extracellular matrix remodeling and increased migratory and metastatic behavior.

In oncology, the Warburg effect is a form of modified cellular metabolism found in cancer cells, which tend to favor a specialised fermentation over the aerobic respiration pathway that most other cells of the body prefer. This observation was first published by Otto Heinrich Warburg who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme".

Pyruvate dehydrogenase lipoamide kinase isozyme 1, mitochondrial is an enzyme that in humans is encoded by the PDK1 gene. It codes for an isozyme of pyruvate dehydrogenase kinase (PDK).

The study of the tumor metabolism, also known as tumor metabolome describes the different characteristic metabolic changes in tumor cells. The characteristic attributes of the tumor metabolome are high glycolytic enzyme activities, the expression of the pyruvate kinase isoenzyme type M2, increased channeling of glucose carbons into synthetic processes, such as nucleic acid, amino acid and phospholipid synthesis, a high rate of pyrimidine and purine de novo synthesis, a low ratio of Adenosine triphosphate and Guanosine triphosphate to Cytidine triphosphate and Uridine triphosphate, low Adenosine monophosphate levels, high glutaminolytic capacities, release of immunosuppressive substances and dependency on methionine.

Lactate dehydrogenase A (LDHA) is an enzyme which in humans is encoded by the LDHA gene. It is a monomer of Lactate dehydrogenase b, which exists as a tetramer. The other main subunit is lactate dehydrogenase B (LDHB).

Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD⁺ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from one molecule to another.

Pyruvate dehydrogenase lipoamide kinase isozyme 4, mitochondrial is an enzyme that in humans is encoded by the PDK4 gene. It codes for an isozyme of pyruvate dehydrogenase kinase.

Forkhead box protein N3 is a protein that in humans is encoded by the FOXN3 gene.

Serine/threonine-protein kinase SIK2 is an enzyme that in humans is encoded by the SIK2 gene.

Formin-binding protein 1-like is a protein that in humans is encoded by the FNBP1L gene.

Lysine-specific demethylase 4B is an enzyme that in humans is encoded by the KDM4B gene. KDM4B belongs to the alpha-ketoglutarate-dependent hydroxylase superfamily.

Zinc finger CCCH-type antiviral protein 1 is a protein that in humans is encoded by the ZC3HAV1 gene.

Formin-like protein 1 is a protein that in humans is encoded by the FMNL1 gene.

TCDD-inducible poly [ADP-ribose] polymerase is an enzyme that in humans is encoded by the TIPARP gene.

Forkhead box protein P4 is a protein that in humans is encoded by the FOXP4 gene.

Pyruvate kinase isozymes M1/M2 (PKM1/M2), also known as pyruvate kinase muscle isozyme (PKM), pyruvate kinase type K, cytosolic thyroid hormone-binding protein (CTHBP), thyroid hormone-binding protein 1 (THBP1), or opa-interacting protein 3 (OIP3), is an enzyme that in humans is encoded by the PKM2 gene.

Semaphorin-6A is a protein that in humans is encoded by the SEMA6A gene.

PDZ domain-containing protein 4 is a protein that in humans is encoded by the PDZD4 gene.

FCH and double SH3 domains protein 1 is a protein that in humans is encoded by the FCHSD1 gene.

Pyruvate dehydrogenase (lipoamide) alpha 2, also known as pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial or PDHE1-A type II, is an enzyme that in humans is encoded by the PDHA2 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000164916 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000056493 - Ensembl, May 2017
↑ "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. PMID 15202027.
↑ "Entrez Gene: FOXK1 forkhead box K1".
1 2 Sukonina, Valentina; Ma, Haixia; Zhang, Wei; Bartesaghi, Stefano; Subhash, Santhilal; Heglind, Mikael; Foyn, Håvard; Betz, Matthias J.; Nilsson, Daniel (Jan 2019). "FOXK1 and FOXK2 regulate aerobic glycolysis". Nature. 566 (7743): 279–283. Bibcode:2019Natur.566..279S. doi:10.1038/s41586-019-0900-5. ISSN 1476-4687. PMID 30700909. S2CID 59524697.

FOXK1

Related Research Articles

References

Further reading