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]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000164916 - Ensembl, May 2017
^ abcGRCm38: 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.
Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC1847948. PMID 17353931.
Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
Tsai KL, Huang CY, Chang CH, et al. (2006). "Crystal structure of the human FOXK1a-DNA complex and its implications on the diverse binding specificity of winged helix/forkhead proteins". J. Biol. Chem. 281 (25): 17400–9. doi:10.1074/jbc.M600478200. PMID 16624804.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC528928. PMID 15489334.
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. PMID 15289879.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Hillier LW, Fulton RS, Fulton LA, et al. (2003). "The DNA sequence of human chromosome 7". Nature. 424 (6945): 157–64. Bibcode:2003Natur.424..157H. doi:10.1038/nature01782. PMID 12853948.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. PMID 12477932.
This article on a gene on human chromosome 7 is a stub. You can help Wikipedia by expanding it.
foxk1, forkhead, protein, transcription, factor, forkhead, family, that, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes2a3s, 2d2widentifiersaliases, forkhead, k1external, idsomim, 616302, 1347488, homologene, 82414, gene. Forkhead box protein K1 is a transcription factor of the forkhead box family that in humans is encoded by the FOXK1 gene 5 6 FOXK1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes2A3S 2D2WIdentifiersAliasesFOXK1 FOXK1L forkhead box K1External IDsOMIM 616302 MGI 1347488 HomoloGene 82414 GeneCards FOXK1Gene location Human Chr Chromosome 7 human 1 Band7p22 1Start4 682 295 bp 1 End4 771 442 bp 1 Gene location Mouse Chr Chromosome 5 mouse 2 Band5 G2 5 81 53 cMStart142 387 252 bp 2 End142 447 766 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed incerebellar vermisinternal globus pallidusponsmiddle temporal gyrussuperior vestibular nucleussubthalamic nucleusBrodmann area 23inferior ganglion of vagus nervesaphenous veinventral tegmental areaTop expressed inascending aortaaortic valvePaneth cellciliary bodycumulus cellretinal pigment epitheliumsupraoptic nucleussecondary oocyteprimitive streaksubmandibular glandMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionDNA binding transcription factor activity DNA binding sequence specific DNA binding RNA polymerase II transcription regulatory region sequence specific DNA binding protein binding DNA binding transcription factor activity RNA polymerase II specific transcription cis regulatory region binding DNA binding transcription activator activity RNA polymerase II specific DNA binding transcription repressor activity RNA polymerase II specificCellular componentnucleus nucleoplasm cytoplasmBiological processregulation 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 IISources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez22193717425EnsemblENSG00000164916ENSMUSG00000056493UniProtP85037P42128RefSeq mRNA NM 001037165NM 010812NM 199068RefSeq protein NP 001032242NP 951031Location UCSC Chr 7 4 68 4 77 MbChr 5 142 39 142 45 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseDuring 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 E1a 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 References edit a b c GRCh38 Ensembl release 89 ENSG00000164916 Ensembl May 2017 a b c 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 a b Sukonina Valentina Ma Haixia Zhang Wei Bartesaghi Stefano Subhash Santhilal Heglind Mikael Foyn Havard 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 Further reading editEwing RM Chu P Elisma F et al 2007 Large scale mapping of human protein protein interactions by mass spectrometry Mol Syst Biol 3 1 89 doi 10 1038 msb4100134 PMC 1847948 PMID 17353931 Olsen JV Blagoev B Gnad F et al 2006 Global in vivo and site specific phosphorylation dynamics in signaling networks Cell 127 3 635 48 doi 10 1016 j cell 2006 09 026 PMID 17081983 S2CID 7827573 Tsai KL Huang CY Chang CH et al 2006 Crystal structure of the human FOXK1a DNA complex and its implications on the diverse binding specificity of winged helix forkhead proteins J Biol Chem 281 25 17400 9 doi 10 1074 jbc M600478200 PMID 16624804 Gerhard DS Wagner L Feingold EA et al 2004 The status quality and expansion of the NIH full length cDNA project the Mammalian Gene Collection MGC Genome Res 14 10B 2121 7 doi 10 1101 gr 2596504 PMC 528928 PMID 15489334 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 PMID 15289879 Ota T Suzuki Y Nishikawa T et al 2004 Complete sequencing and characterization of 21 243 full length human cDNAs Nat Genet 36 1 40 5 doi 10 1038 ng1285 PMID 14702039 Hillier LW Fulton RS Fulton LA et al 2003 The DNA sequence of human chromosome 7 Nature 424 6945 157 64 Bibcode 2003Natur 424 157H doi 10 1038 nature01782 PMID 12853948 Strausberg RL Feingold EA Grouse LH et al 2003 Generation and initial analysis of more than 15 000 full length human and mouse cDNA sequences Proc Natl Acad Sci U S A 99 26 16899 903 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 nbsp This article on a gene on human chromosome 7 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title FOXK1 amp oldid 1107451526, wikipedia, wiki, book, books, library,
