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Comment
. 2018 May;29(5):281-282.
doi: 10.1016/j.tem.2018.02.005. Epub 2018 Feb 20.

Taking Aim at Glycolysis with CDK8 Inhibitors

Robert P Fisher  1
Affiliations
Comment

Taking Aim at Glycolysis with CDK8 Inhibitors

Robert P Fisher. Trends Endocrinol Metab. 2018 May.

Abstract

Dependence on glycolysis under aerobic conditions, a frequent metabolic derangement in cancer cells, suggests a therapeutic opportunity. Now, through chemical genetics, CDK8, a kinase associated with the Mediator transcriptional coactivator complex, has emerged as an upstream inducer of glycolysis and a possible target for anticancer drug discovery.

Keywords: CDK8; Mediator; cancer; chemical genetics; glycolysis; transcription.

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Figures

Figure 1
Figure 1. CDK8, a druggable target in aerobic glycolysis?
Expression of glycolytic-pathway genes depends on the co-activator function of CDK8-Mediator, which transmits transcription-stimulatory signals from hypoxia-inducible factor 1A (HIF1A), bound at its response element (RE), to the promoter-bound, Pol II-containing pre-initiation complex (PIC). This pathway of transcriptional activation is normally triggered by hypoxia but becomes constitutively active in cancer cells, potentially sensitizing them to small-molecule inhibition of CDK8, the only known enzymatic function within the CDK8-Mediator complex.
See this image and copyright information in PMC

Comment on

  • CDK8 Kinase Activity Promotes Glycolysis.
    Galbraith MD, Andrysik Z, Pandey A, Hoh M, Bonner EA, Hill AA, Sullivan KD, Espinosa JM. Galbraith MD, et al. Cell Rep. 2017 Nov 7;21(6):1495-1506. doi: 10.1016/j.celrep.2017.10.058. Cell Rep. 2017. PMID: 29117556 Free PMC article.

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