Advance in Transcriptional Regulation by Conventional Metabolic Enzymes
A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".
Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 3642
Special Issue Editor
Special Issue Information
Dear Colleagues,
Recently, many conventional metabolic enzymes are localized in nucleus, where they play novel non-conventional functions in nucleus including particularly transcriptional regulation through epigenetic modifications.
Pyruvate dehydrogenase complex (PDC) in nucleus can provide acetyl-coA, which is used for histone acetylation to regulate gene expression. Remarkably, ATP citrate lyase in nucleus, which catalyzes cleavage of citrate plus CoA to acetyl-CoA plus oxaloacetate, is involved in histone acetylation of epigenetic regulation.
Pyruvate kinase M2 (PKM2) in nucleus plays a conventional function to provide pyruvate, which is used for acetyl-CoA production to modify histone protein and a non-conventional function of protein kinase to phosphorylate histone protein and STAT3. In addition, PKM2 bins with HIF-1α and Oct4, regulating gene expression as a co-transcription factor.
Phosphofructokinase 1 (PFK1) binds to the transcriptional coactivator TEADS to stabilizes YAP/TAZ. PFK3B binds to Cdk1, cyclin D3 and Cdc25C. PFK1 product fructose-2,6-bisphosphate is used for the phosphorylation of p27 by Cdk1, undergoing p27 degradation.
Fructose-1,6-bisphosphate Aldolase (ALDO) binds to DNA and interacts with RNA polymerase III. Fructose-1,6-bisphosphatase (FBP1) interacts with HIF-1α, inhibiting its transcriptional activity.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) binds to Oc1 and Oct1 coactivator in S phase (OCA-S), promoting the expression of histone H2B in S-phase. In addition, GAPDH protects and maintains telomeres.
Phosphofructokinase (PGK) is an accessory protein for DNA polymerase α. Enolase binds to DNA and regulates c-Myc expression. Enolase interacts with the transcription factors activated Notch1 receptor on c-My promoter.
Lactate dehydrogenase (LDH) interacts with DNA polymerase αδε, stimulating DNA synthesis. Of interest, nuclear LDH binds to sirtuin 1, increasing sirtuin 1 activity through LDH-mediated produced NAD.
In addition, some mitochondrial enzymes in the Krebs cycle, including succinate dehydrogenase (SDH), fumarase, malate dehydrogenase, aconitase, isocitrate dehydrogenase (IDH), are also localized in nucleus and play non-conventional functions in nucleus. Fumarase participates in DNA repair and IDH is involved in histone and DNA methylation. Malate dehydrogenase regulates p53 transcriptional activity.
Additionally, methyltransferase, s-adenosylmethione (SAM) and demethylase regulate DNA and histone methylation levels. α-Ketoglutarate is required for histone and DNA demethylase as a cofactor. Accordingly, metabolic enzyme to produce similar metabolites including fumarate and succinate as α-ketoglutarate can inhibits demethylase activity as competitive inhibitors. Furthermore, 2-hydoxyglutarate regulates the transcriptional activity of HIF or inhibits enzymes involved in DNBA repair in cancer.
In this Special Issue, we would like to publish new papers related to “Advance in Transcriptional Regulation by Conventional Metabolic Enzymes”.
Dr. Jae-Bong Park
Guest Editor
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Keywords
- metabolic enzymes
- nuclear translocation
- transcription factor
- transcriptional regulation
- epigenetic modification
- acetylation of DNA and histone
- methylation of DNA and histone
- metabolite
