ArticleOncogene2023
PCNA regulates primary metabolism by scaffolding metabolic enzymes.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Deciphering the cellular landscape and genetic underpinnings of fiber diameter determined by dermal papilla cells in fine-wool sheep.Frontiers in cell and developmental biology · 2026Article
- Targeting PCNA in Cancer: A Paradigm Shift from Static Inhibition to Dynamic Network Modulation.Oncology research · 2026Review
- Effects ofAnimals : an open access journal from MDPI · 2025Article
- A dual-mechanism antimicrobial peptide with antimutagenic activity targets the replisome and induces cell envelope stress.mSphere · 2025Article
- DNA Damage Repair in Glioblastoma: A Novel Approach to Combat Drug Resistance.Cell proliferation · 2025Article
- Tissue-Specific Expression of the PorcineAnimals : an open access journal from MDPI · 2025Article
- AOH1996 targets mitochondrial dynamics and metabolism in leukemic stem cells via mitochondrial PCNA inhibition.Experimental hematology & oncology · 2024Article
- Article
- A triterpenoid (corosolic acid) ameliorated AOM-mediated aberrant crypt foci in rats: modulation of Bax/PCNA, antioxidant and inflammatory mechanisms.Journal of molecular histology · 2024Article
- LncRNA MAGI2-AS3-Encoded Polypeptide Restrains the Proliferation and Migration of Breast Cancer Cells.Molecular biotechnology · 2024Article
- The bacterial DNA sliding clamp, β-clamp: structure, interactions, dynamics and drug discovery.Cellular and molecular life sciences : CMLS · 2024Review
- Activation of multiple stress responses inFrontiers in microbiology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The essential roles of proliferating cell nuclear antigen (PCNA) as a scaffold protein in DNA replication and repair are well established, while its cytosolic roles are less explored. Two metabolic enzymes, alpha-enolase (ENO1) and 6-phosphogluconate dehydrogenase (6PGD), both contain PCNA interacting motifs. Mutation of the PCNA interacting motif APIM in ENO1 (F423A) impaired its binding to PCNA and resulted in reduced cellular levels of ENO1 protein, reduced growth rate, reduced glucose consumption, and reduced activation of AKT. Metabolome and signalome analysis reveal large consequences of impairing the direct interaction between PCNA and ENO1. Metabolites above ENO1 in glycolysis accumulated while lower glycolytic and TCA cycle metabolite pools decreased in the APIM-mutated cells; however, their overall energetic status were similar to parental cells. Treating haematological cancer cells or activated primary monocytes with a PCNA targeting peptide drug containing APIM (ATX-101) also lead to a metabolic shift characterized by reduced glycolytic rate. In addition, we show that ATX-101 treatments reduced the ENO1 - PCNA interaction, the ENO1, GAPDH and 6PGD protein levels, as well as the 6PGD activity. Here we report for the first time that PCNA acts as a scaffold for metabolic enzymes, and thereby act as a direct regulator of primary metabolism.
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Registered trials
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 OpenQuestion graph.