Evidence map›Paper›PMID 35708495›Full record

ArticleGlycobiology2022

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

Aishwarya Gondane, Ninu Poulose, Suzanne Walker, Ian G Mills, Harri M Itkonen

Open access · hybridAbstract read
In one paragraph

Article in Glycobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. OGT and OGA: Sweet guardians of the genome.The Journal of biological chemistry · 2024
    Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 3 countries.

Aishwarya GondaneDepartment of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland.
Ninu PoulosePatrick G Johnston Centre for Cancer Research, Queen's University, Belfast BT9 7AE, United Kingdom.
Suzanne WalkerDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, United States.
Ian G MillsPatrick G Johnston Centre for Cancer Research, Queen's University, Belfast BT9 7AE, United Kingdom.
Harri M ItkonenDepartment of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland.ORCID 0000-0002-5194-7064
Queen's University Belfast · GBUniversity of Helsinki · FIHarvard University · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Structure, Function and Inhibition of Human O-GlcNAc TransferaseR01GM094263 · NIGMS · HARVARD MEDICAL SCHOOL · PI WALKER, SUZANNE · 2012 to 2024
$5.8M
NCI NIH HHS P30 CA016672NIGMS NIH HHS R01 GM094263
6 · The paper itself

Abstract

Co-targeting of O-GlcNAc transferase (OGT) and the transcriptional kinase cyclin-dependent kinase 9 (CDK9) is toxic to prostate cancer cells. As OGT is an essential glycosyltransferase, identifying an alternative target showing similar effects is of great interest. Here, we used a multiomics approach (transcriptomics, metabolomics, and proteomics) to better understand the mechanistic basis of the combinatorial lethality between OGT and CDK9 inhibition. CDK9 inhibition preferentially affected transcription. In contrast, depletion of OGT activity predominantly remodeled the metabolome. Using an unbiased systems biology approach (weighted gene correlation network analysis), we discovered that CDK9 inhibition alters mitochondrial activity/flux, and high OGT activity is essential to maintain mitochondrial respiration when CDK9 activity is depleted. Our metabolite profiling data revealed that pantothenic acid (vitamin B5) is the metabolite that is most robustly induced by both OGT and OGT+CDK9 inhibitor treatments but not by CDK9 inhibition alone. Finally, supplementing prostate cancer cell lines with vitamin B5 in the presence of CDK9 inhibitor mimics the effects of co-targeting OGT and CDK9.

Indexed as

Cyclin-Dependent Kinase 9Prostatic NeoplasmsHomeostasisHumansMaleN-AcetylglucosaminyltransferasesPantothenic AcidCDK9 protein, humanCyclin-Dependent Kinase 9N-AcetylglucosaminyltransferasesO-GlcNAc transferasePantothenic Acidcyclin-dependent kinase 9metabolismO-GlcNAc transferaseprostate cancersystems biology

Identifiers

PMID35708495
PMCPMC9387508
OpenAlexW4283013249

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.