O-GlcNAc Transferase - An Auxiliary Factor or a Full-blown Oncogene?
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
19
10
2020
revised:
05
12
2020
accepted:
07
01
2021
pubmed:
22
1
2021
medline:
13
1
2022
entrez:
21
1
2021
Statut:
ppublish
Résumé
The β-linked N-acetyl-d-glucosamine (GlcNAc) is a posttranslational modification of serine and threonine residues catalyzed by the enzyme O-GlcNAc transferase (OGT). Increased OGT expression is a feature of most human cancers and inhibition of OGT decreases cancer cell proliferation. Antiproliferative effects are attributed to posttranslational modifications of known regulators of cancer cell proliferation, such as MYC, FOXM1, and EZH2. In general, OGT amplifies cell-specific phenotype, for example, OGT overexpression enhances reprogramming efficiency of mouse embryonic fibroblasts into stem cells. Genome-wide screens suggest that certain cancers are particularly dependent on OGT, and understanding these addictions is important when considering OGT as a target for cancer therapy. The O-GlcNAc modification is involved in most cellular processes, which raises concerns of on-target undesirable effects of OGT-targeting therapy. Yet, emerging evidence suggest that, much like proteasome inhibitors, specific compounds targeting OGT elicit selective antiproliferative effects in cancer cells, and can prime malignant cells to other treatments. It is, therefore, essential to gain mechanistic insights on substrate specificity for OGT, develop reagents to more specifically enrich for O-GlcNAc-modified proteins, identify O-GlcNAc "readers," and develop OGT small-molecule inhibitors. Here, we review the relevance of OGT in cancer progression and the potential targeting of this metabolic enzyme as a putative oncogene.
Identifiants
pubmed: 33472950
pii: 1541-7786.MCR-20-0926
doi: 10.1158/1541-7786.MCR-20-0926
doi:
Substances chimiques
N-Acetylglucosaminyltransferases
EC 2.4.1.-
O-GlcNAc transferase
EC 2.4.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
555-564Subventions
Organisme : Prostate Cancer UK
ID : CEO13_2-004
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA187918
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA211024
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
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