ArticleOncogene2022
Histone N-terminal acetyltransferase NAA40 links one-carbon metabolism to chemoresistance.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Histone and Histone Acetylation-Related Alterations of Gene Expression in Uninvolved Psoriatic Skin and Their Effects on Cell Proliferation, Differentiation, and Immune Responses.International journal of molecular sciences · 2023Pooled it
- NatD promotes glioblastoma progression through epigenetic activation of FGFR4 signalling.Experimental & molecular medicine · 2026Article
- NAA40 and NAC cooperate in co-translational histone acetylation in humans.Nature communications · 2026Article
- A Cell-Potent Bisubstrate Inhibitor to Probe NatD Acetyltransferase Activity.ACS chemical biology · 2025Article
- Deciphering Autoantigen Signatures in Chikungunya Virus Infection Using Machine Learning: A Data-Driven Approach to Understand Host Immunity.Current microbiology · 2025Article
- Crosstalk Between Metabolic Reprogramming and Epigenetic Modifications in Colorectal Cancer: Mechanisms and Clinical Applications.Current issues in molecular biology · 2025Review
- H2A.X N-terminal acetylation is a newly identified NAA40-mediated modification that is responsive to UV irradiation.Epigenetics & chromatin · 2025Article
- Illuminating the impact of N-terminal acetylation: from protein to physiology.Nature communications · 2025Review
- RNF112, whose transcription is regulated by KLF4, inhibits colorectal cancer growth via promoting ubiquitin-dependent degradation of NAA40.Cell biology and toxicology · 2025Article
- Metabolism and epigenetics in cancer: toward personalized treatment.Frontiers in endocrinology · 2025Review
- Purification and activity assays of N-terminal acetyltransferase D.Methods in enzymology · 2025Article
- Integration of multi-omics summary data reveals the role of N6-methyladenosine in neuropsychiatric disorders.Molecular psychiatry · 2024Article
- Yeast Nat4 regulates DNA damage checkpoint signaling through its N-terminal acetyltransferase activity on histone H4.PLoS genetics · 2024Article
- Biochemical Characterisation of the Short Isoform of Histone N-Terminal Acetyltransferase NAA40.Biomolecules · 2024Article
- Synergistic Mechanisms of Selected Polyphenols in Overcoming Chemoresistance and Enhancing Chemosensitivity in Colorectal Cancer.Antioxidants (Basel, Switzerland) · 2024Review
- NatD epigenetically activates FOXA2 expression to promote breast cancer progression by facilitating MMP14 expression.iScience · 2024Article
- Unlocking the potential of targeting histone-modifying enzymes for treating IBD and CRC.Clinical epigenetics · 2023Review
- Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant function of epigenetic modifiers plays an important role not only in the progression of cancer but also the development of drug resistance. N-alpha-acetyltransferase 40 (NAA40) is a highly specific epigenetic enzyme catalyzing the transfer of an acetyl moiety at the N-terminal end of histones H4 and H2A. Recent studies have illustrated the essential oncogenic role of NAA40 in various cancer types but its role in chemoresistance remains unclear. Here, using transcriptomic followed by metabolomic analysis in colorectal cancer (CRC) cells, we demonstrate that NAA40 controls key one-carbon metabolic genes and corresponding metabolites. In particular, through its acetyltransferase activity NAA40 regulates the methionine cycle thereby affecting global histone methylation and CRC cell survival. Importantly, NAA40-mediated metabolic rewiring promotes resistance of CRC cells to antimetabolite chemotherapy in vitro and in xenograft models. Specifically, NAA40 stimulates transcription of the one-carbon metabolic gene thymidylate synthase (TYMS), whose product is targeted by 5-fluorouracil (5-FU) and accordingly in primary CRC tumours NAA40 expression associates with TYMS levels and poorer 5-FU response. Mechanistically, NAA40 activates TYMS by preventing enrichment of repressive H2A/H4S1ph at the nuclear periphery. Overall, these findings define a novel regulatory link between epigenetics and cellular metabolism mediated by NAA40, which is harnessed by cancer cells to evade chemotherapy.
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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.