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Literature summary for 2.7.11.2 extracted from
- p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2 (2012), Cancer Res., 72, 560-567.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| acetyl-CoA | Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase | Homo sapiens |  |
| NADH | Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase | Homo sapiens | |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| expression in HCT-116 cells | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| P53 | negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2 | Homo sapiens | |
| P53 | negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2 | Mus musculus | |
| pyruvate | Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase | Homo sapiens | |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | rquired | Mus musculus | |
| Mg2+ | rquired | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + [pyruvate dehydrogenase (acetyl-transferring)] | Mus musculus | - |
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate | - |
? | |
| ATP + [pyruvate dehydrogenase (acetyl-transferring)] | Homo sapiens | - |
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Mus musculus | - |
- |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| carcinoma cell | - |
Mus musculus | - |
| carcinoma cell | - |
Homo sapiens | - |
| EB-1 cell | - |
Homo sapiens | - |
| HCT-116 cell | - |
Homo sapiens | - |
| MCF-7 cell | MCF-7 cells do not express mRNA for pdk4, but express Pdk2 | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + [pyruvate dehydrogenase (acetyl-transferring)] | - |
Mus musculus | ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate | - |
? | |
| ATP + [pyruvate dehydrogenase (acetyl-transferring)] | - |
Homo sapiens | ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| PDK2 | - |
Mus musculus |
| PDK2 | - |
Homo sapiens |
| pyruvate dehydrogenase kinase | - |
Mus musculus |
| pyruvate dehydrogenase kinase | - |
Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Mus musculus | |
| ATP | - |
Homo sapiens | |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Homo sapiens | Pdk2 transcription decreases upon addition of nutlin-3a, nutlin-3a can produce off-target effects, upon reduction of p53, the effect of nutlin-3a upon Pdk2 protein decreases. A histone deacetylase inhibitor, trichostatin A, partially prevents repression of Pdk2 transcription by p53 | down |
| Mus musculus | the amount of Pdk2 mRNA in both colon and spleen decreases upon irradiation of wild-type mice but not upon irradiation of p53 knockout mice, p53 decreases Pdk2 transcription in vivo | down |
| Homo sapiens | cotransfection with plasmids expressing either E2F1 or E2F2 activates Pdk2/luciferase transcription. E2F1 binds less well to the Pdk2 promoter when p53 is induced with zinc | up |
General Information
| General Information | Comment | Organism |
|---|---|---|
| metabolism | p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2, which negatively regulates the pyruvate dehydrogenase complex. Decreased levels of Pdk2 and P-Pdc in turn promote conversion of pyruvate into acetyl-CoA instead of lactate | Mus musculus |
| metabolism | p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2, which negatively regulates the pyruvate dehydrogenase complex. Decreased levels of Pdk2 and P-Pdc in turn promote conversion of pyruvate into acetyl-CoA instead of lactate | Homo sapiens |
| physiological function | Pdk2 is seen as the key control point in conversion of pyruvate to acetyl-CoA reaction because it responds allosterically to rapid local changes in substrate and product: Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase | Mus musculus |
| physiological function | Pdk2 is seen as the key control point in conversion of pyruvate to acetyl-CoA reaction because it responds allosterically to rapid local changes in substrate and product: Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase. P53-dependent apoptosis requires downregulation of Pdk2, early apoptotic events do not occur unless p53 can downregulate the transcription of Pdk2 | Homo sapiens |
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