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Updated: Sep 7, 2025

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
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Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases

Published on: October 10, 2020

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O-GlcNAc transferase maintains metabolic homeostasis in response to CDK9 inhibition

Aishwarya Gondane1, Ninu Poulose2,3, Suzanne Walker4

  • 1Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland.

Glycobiology
|June 16, 2022
PubMed

Insights

Combining O-GlcNAc transferase (OGT) and cyclin-dependent kinase 9 (CDK9) inhibition is toxic to prostate cancer. Vitamin B5 supplementation mimics this combined effect with CDK9 inhibition, offering a potential therapeutic strategy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Co-targeting O-GlcNAc transferase (OGT) and cyclin-dependent kinase 9 (CDK9) demonstrates toxicity in prostate cancer cells.
  • OGT is an essential glycosyltransferase, making the identification of alternative therapeutic targets crucial.

Purpose of the Study:

  • To elucidate the mechanistic underpinnings of the combined lethality induced by OGT and CDK9 inhibition.
  • To explore the distinct and overlapping roles of OGT and CDK9 in prostate cancer cell biology.

Main Methods:

  • Utilized a multiomics approach, including transcriptomics, metabolomics, and proteomics.
  • Employed weighted gene correlation network analysis (WGCNA) for systems biology insights.
  • Conducted metabolite profiling and cell-based supplementation assays.

Main Results:

  • CDK9 inhibition primarily impacted transcription, while OGT depletion significantly remodeled the metabolome.
  • CDK9 inhibition disrupted mitochondrial activity, and OGT activity was vital for maintaining mitochondrial respiration under CDK9 inhibition.
  • Pantothenic acid (vitamin B5) was identified as a key metabolite induced by OGT inhibition and combined OGT/CDK9 inhibition.

Conclusions:

  • High OGT activity is essential for maintaining mitochondrial function when CDK9 is inhibited.
  • Supplementation with vitamin B5 alongside CDK9 inhibition effectively replicates the cytotoxic effects of simultaneously targeting OGT and CDK9 in prostate cancer cells.
  • This suggests a potential therapeutic avenue involving vitamin B5 and CDK9 inhibitors for prostate cancer treatment.
Keywords:
O-GlcNAc transferasecyclin-dependent kinase 9metabolismprostate cancersystems biology

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