GO:0016453 C-acetyltransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0016453 C-acetyltransferase activity describes the catalysis of acetyl group transfer to a carbon atom on an acceptor molecule, a fundamental protein modification.
• Key enzymes include ACAT1, which acetylates ME2 and affects chemoresistance in ovarian cancer, and NAT10, which acetylates RNA and drives glycolysis in triple-negative breast cancer.
• C-acetyltransferase activity regulates diverse cellular processes such as cholesterol metabolism, lipid synthesis, and immune responses.
• Dysregulation of C-acetyltransferase activity is implicated in cancer, neurodegeneration, and metabolic disorders.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) are essential to dissect the causal roles of C-acetyltransferases.
• EDITGENE provides comprehensive CRISPR services to study C-acetyltransferase activity, from library screening to bioinformatics.
Description
C-acetyltransferase activity (GO:0016453) is a molecular function defined as the catalysis of the transfer of an acetyl group to a carbon atom on an acceptor molecule. This enzymatic activity is central to post-translational modifications and metabolic regulation, influencing protein stability, localization, and interactions. Researchers study C-acetyltransferases to understand how acetylation modulates cellular pathways in health and disease. For example, ACAT1 acetylates ME2 to drive chemoresistance in ovarian cancer, while NAT10 acetylates RNA to promote glycolysis in triple-negative breast cancer. These findings underscore the importance of C-acetyltransferase activity in cancer metabolism and beyond. This article synthesizes authoritative QuickGO data and verified PubMed literature to provide a research-grade overview of GO:0016453, covering its mechanism, key genes, disease relevance, and experimental approaches.
C-acetyltransferase activity At A Glance
| GO ID | GO:0016453 |
|---|---|
| GO term | C-acetyltransferase activity |
| Ontology | molecular_function |
| Synonym | None |
| Definition | Catalysis of the transfer of an acetyl group to a carbon atom on the acceptor molecule. |
| Major function | Acetylation of carbon atoms in proteins, lipids, and other molecules |
| Related enzymes | ACAT1, NAT10, and other acetyltransferases |
| Cellular context | Cytoplasm, nucleus, mitochondria |
| Disease relevance | Cancer, neurodegeneration, metabolic disorders |
What Is GO:0016453?
C-acetyltransferase activity (GO:0016453) is the catalysis of the transfer of an acetyl group to a carbon atom on the acceptor molecule. This activity is distinct from N-acetyltransferases, which transfer acetyl groups to nitrogen atoms. The reaction typically involves acetyl-CoA as the acetyl donor, and the acceptor can be a protein, lipid, or other small molecule. This modification can alter the charge, structure, and function of the target molecule, thereby impacting various biological processes.
Why Is C-acetyltransferase activity Important in Cell Biology?
C-acetyltransferase activity is crucial for cellular homeostasis because acetylation regulates enzyme activity, protein-protein interactions, and metabolic flux. Dysregulation of this activity contributes to cancer progression, immune evasion, and neurodegenerative diseases. Understanding the molecular mechanisms and identifying specific C-acetyltransferases can reveal therapeutic targets and biomarkers.
• Regulates protein function and stability through acetylation.
• Modulates cholesterol metabolism and lipid homeostasis.
• Drives cancer chemoresistance and metabolic reprogramming.
• Influences immune responses, including NK cell antitumor immunity.
• Affects brain inflammatory profiles in aging and neurodegeneration.
• Plays a role in osteonecrosis of the femoral head via lipid production.
• Provides potential targets for cancer therapy and metabolic diseases.
• Enables research into post-translational modifications and epigenetics.
• Facilitates the development of CRISPR-based disease models.
• Offers opportunities for drug discovery targeting acetyltransferases.
What Happens During C-acetyltransferase activity?
Substrate Recognition and Binding
In simple terms: The enzyme first grabs the molecule it will modify.
C-acetyltransferases recognize specific acceptor molecules, such as proteins or lipids, through structural motifs. For instance, ACAT1 binds to ME2 to acetylate it, impacting glutaminolysis and lactate production. NAT10 recognizes RNA substrates for ac4C modification.
Acetyl Group Transfer
In simple terms: The enzyme moves an acetyl group onto the target molecule.
Using acetyl-CoA as a donor, the enzyme transfers the acetyl group to a carbon atom on the acceptor. This reaction is catalyzed by a conserved catalytic domain. For example, ACAT1 acetylates ME2 at specific lysine residues, altering its activity.
Conformational Change and Release
In simple terms: The modified molecule is released, and the enzyme resets.
After acetylation, the modified acceptor undergoes conformational changes that affect its function. The enzyme releases the product and is ready for another cycle. This dynamic regulation is seen in cholesterol metabolism where ACAT1 activity modulates lipid storage.
Downstream Signaling and Metabolic Effects
In simple terms: The acetylated molecule then triggers changes in the cell.
Acetylation can alter protein interactions, enzymatic activity, or localization, leading to downstream effects such as enhanced glycolysis in cancer cells or altered immune responses. These effects contribute to disease phenotypes like chemoresistance.
Key Genes Involved in GO:0016453 C-acetyltransferase activity
The following genes encode enzymes with C-acetyltransferase activity or are directly regulated by it, as supported by verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ACAT1 | Acetylates ME2, regulates cholesterol metabolism | Ovarian cancer chemoresistance, lipid metabolism |
| NAT10 | RNA acetyltransferase (ac4C) | Triple-negative breast cancer glycolysis and immunosuppression |
| ACAT1 (mitochondrial) | Acetyl-CoA acetyltransferase | NK cell antitumor immunity in colorectal cancer |
| ME1 | Malic enzyme 1, regulated by acetylation | Lipid metabolism and colorectal tumorigenesis |
| ME2 | Malic enzyme 2, acetylated by ACAT1 | Glutaminolysis and lactate production in ovarian cancer |
| TREM2 | Regulates microglial cholesterol metabolism | Chronic phagocytic challenge and neurodegeneration |
| SOAT1 | Cholesterol storage enzyme | Aging and brain inflammatory profiles |
| HMGCR | Cholesterol synthesis | Osteonecrosis of the femoral head |
| STK11 | Serine/threonine kinase | Osteonecrosis and lipid production |
| NAMPT | NAD biosynthesis | Osteonecrosis and lipid production |
| JunB | Transcription factor | TNBC progression and immunosuppression |
| CD8+ T cells | Immune cells | Antitumour response via cholesterol metabolism |
| NK cells | Natural killer cells | Antitumor immunity in colorectal cancer |
| Microglia | Brain immune cells | Cholesterol metabolism and inflammation |
| Apolipoprotein E4 | Lipid transport | Brain inflammatory profiles in aging |
| ACAT1/SOAT1 | Cholesterol storage | Inhibiting alters brain inflammatory profiles |
| ME1/ME2 | Malic enzymes | Acetylation affects lipid metabolism and tumorigenesis |
How Is C-acetyltransferase activity Regulated?
C-acetyltransferase activity is regulated at multiple levels. Enzyme expression can be induced by metabolic stress or immune signals. Post-translational modifications of the enzymes themselves, such as phosphorylation, can modulate their activity. Additionally, substrate availability and cofactor levels (e.g., acetyl-CoA) influence the rate of acetylation. In cancer, oncogenic signaling pathways can upregulate acetyltransferases like NAT10 to promote glycolysis. Conversely, inhibiting ACAT1/SOAT1 alters inflammatory profiles in the brain, suggesting that enzyme activity is tightly linked to lipid metabolism.
C-acetyltransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ACAT1 | Ovarian cancer chemoresistance | Knockout in ovarian cancer cell lines |
| NAT10 | Triple-negative breast cancer | Knockdown or knockout in TNBC cells |
| ACAT1 | Colorectal cancer immunity | Conditional knockout in mouse models |
| TREM2 | Neurodegeneration | Knockout in microglial cells |
| ACAT1/SOAT1 | Alzheimer's disease | Inhibitor treatment in APOE4 mice |
Cancer
C-acetyltransferase activity is frequently dysregulated in cancer. ACAT1-mediated acetylation of ME2 drives chemoresistance in ovarian cancer by linking glutaminolysis to lactate production. NAT10 acetylates RNA to facilitate TNBC malignant progression and immunosuppression by driving glycolysis addiction. Mitochondrial ACAT1 orchestrates NK cell-dependent antitumor immunity in colorectal cancer. These findings highlight acetyltransferases as potential therapeutic targets.
Neurodegeneration and Aging
In the brain, C-acetyltransferase activity impacts cholesterol metabolism and inflammation. TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge, linking to neurodegeneration. Inhibiting ACAT1/SOAT1 in aging apolipoprotein E4 mice alters brain inflammatory profiles, suggesting a role in Alzheimer's disease.
Metabolic and Bone Disorders
ACAT1 is involved in lipid production associated with nontraumatic osteonecrosis of the femoral head. The NAMPT/STK11/HMGCR/ACAT1 axis mediates lipid production, and its inhibition repairs the condition. Additionally, dynamic regulation of ME1 phosphorylation and acetylation affects lipid metabolism and colorectal tumorigenesis.
Immune Regulation
Modulating cholesterol metabolism in CD8+ T cells potentiates antitumour responses. This suggests that C-acetyltransferase activity, through cholesterol esterification, can influence immune cell function and cancer immunotherapy.
From C-acetyltransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does ACAT1 acetylation of ME2 drive chemoresistance? | Point mutation of ME2 acetylation sites |
| What is the role of NAT10 in TNBC glycolysis? | Knockout of NAT10 in TNBC cell lines |
| How does mitochondrial ACAT1 affect NK cell immunity? | Conditional knockout in colorectal cancer models |
| Does TREM2 regulate microglial cholesterol metabolism? | Knockout of TREM2 in microglia |
| Can inhibiting ACAT1 alter brain inflammation? | Overexpression of ACAT1 in APOE4 mice |
| What is the impact of ME1 acetylation on tumorigenesis? | Knock-in of acetylation-deficient ME1 |
How to Study the C-acetyltransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR-Cas9 knockout | Loss-of-function phenotypes | Identifying essential acetyltransferases |
| Point mutation | Specific acetylation site function | Dissecting ME2 acetylation in chemoresistance |
| Knock-in | Introduction of mutant alleles | Studying acetylation-deficient enzymes |
| Overexpression | Gain-of-function effects | Assessing ACAT1 role in brain inflammation |
| RNA-seq | Transcriptional changes | Pathway analysis after NAT10 knockout |
| Proteomics | Acetylome profiling | Global acetylation changes |
| CRISPR library screening | Gene networks | Identifying modifiers of acetylation |
| Bioinformatics | Pathway enrichment | Interpreting acetylation data |
CRISPR-Cas9 Knockout
Knockout of C-acetyltransferase genes (e.g., ACAT1, NAT10) using CRISPR-Cas9 allows researchers to assess loss-of-function phenotypes. For example, ACAT1 knockout in ovarian cancer cells reduced ME2 acetylation and chemoresistance. NAT10 knockout in TNBC cells impaired glycolysis and tumor progression.
Point Mutation and Knock-in
Introducing point mutations at acetylation sites (e.g., ME2 lysine residues) or knock-in of acetylation-deficient enzymes can dissect the specific contribution of acetylation. This approach was used to show that ACAT1-mediated ME2 acetylation drives chemoresistance.
Overexpression and Tagged Knock-in
Overexpressing wild-type or mutant C-acetyltransferases, or tagging them with fluorescent proteins, enables live-cell imaging and biochemical assays. For instance, overexpression of ACAT1 in APOE4 mice altered brain inflammatory profiles.
Library Screening and Bioinformatics
CRISPR library screening can identify genes that modulate C-acetyltransferase activity or its downstream effects. Bioinformatics analysis of acetylation sites and pathways (e.g., KEGG, GO) helps interpret high-throughput data.
How CRISPR Can Be Used to Study GO:0016453 C-acetyltransferase activity
Knockout
CRISPR knockout of C-acetyltransferase genes (e.g., ACAT1, NAT10) is used to study their essential roles in cancer and metabolism. For example, ACAT1 knockout reduced ME2 acetylation and chemoresistance in ovarian cancer, while NAT10 knockout impaired TNBC glycolysis.
Point Mutation
Point mutations at acetylation sites (e.g., ME2 K residues) or catalytic residues of acetyltransferases can reveal specific functions. This approach demonstrated that ACAT1-mediated ME2 acetylation drives chemoresistance.
Knock-in
Knock-in of acetylation-deficient or -mimetic alleles allows precise control of acetylation status. For instance, knock-in of ME1 acetylation mutants affected lipid metabolism and tumorigenesis.
Overexpression
Overexpression of wild-type or mutant C-acetyltransferases (e.g., ACAT1) in cell lines or mouse models can elucidate gain-of-function effects, such as altered brain inflammatory profiles in APOE4 mice.
How EDITGENE Supports C-acetyltransferase activity Research
Researchers studying C-acetyltransferase activity-related genes often need to determine whether a candidate gene is causally involved in a specific phenotype, such as chemoresistance or immune evasion. This requires precise genetic manipulation, which EDITGENE provides through its comprehensive CRISPR services.
Contact EDITGENE today to design your custom CRISPR model for C-acetyltransferase activity research.
Frequently Asked Questions About C-acetyltransferase activity
What is C-acetyltransferase activity?
C-acetyltransferase activity (GO:0016453) is the catalysis of the transfer of an acetyl group to a carbon atom on an acceptor molecule, a key post-translational modification.
What genes are involved in C-acetyltransferase activity?
Key genes include ACAT1, NAT10, and others that encode enzymes with this activity, as well as substrates like ME2.
How is C-acetyltransferase activity regulated?
It is regulated by enzyme expression, post-translational modifications, substrate availability, and metabolic signals.
What diseases are associated with C-acetyltransferase activity?
Dysregulation is linked to cancer (ovarian, breast, colorectal), neurodegeneration, and metabolic bone disorders.
What methods are used to study C-acetyltransferase activity?
CRISPR knockout, point mutation, knock-in, overexpression, proteomics, and bioinformatics are commonly used.
How does ACAT1 contribute to cancer?
ACAT1 acetylates ME2 to drive chemoresistance in ovarian cancer and affects NK cell immunity in colorectal cancer.
What is the role of NAT10 in cancer?
NAT10 acetylates RNA to promote glycolysis and immunosuppression in triple-negative breast cancer.
Can C-acetyltransferase activity be targeted therapeutically?
Yes, inhibitors of ACAT1/SOAT1 have shown effects in brain inflammation and cancer models.
What is the difference between C-acetyltransferase and N-acetyltransferase?
C-acetyltransferase transfers acetyl groups to carbon atoms, while N-acetyltransferase transfers to nitrogen atoms.
How can EDITGENE help with C-acetyltransferase research?
EDITGENE provides CRISPR knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics services to study C-acetyltransferase activity.
Conclusion
C-acetyltransferase activity (GO:0016453) is a fundamental molecular function with broad implications in cancer, neurodegeneration, and metabolic diseases. The verified literature highlights key enzymes like ACAT1 and NAT10 and their roles in acetylation-driven pathologies. Leveraging CRISPR-based models and advanced bioinformatics, researchers can dissect the causal roles of these enzymes and develop targeted therapies. EDITGENE stands ready to support these efforts with comprehensive gene editing services.
References
- 1. Nugent AA et al.. 2020. TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge.. Neuron 105(5):837-854.e9 PMID: 31902528
- 2. Yang W et al.. 2016. Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism.. Nature 531(7596):651-5 PMID: 26982734
- 3. Zheng C et al.. 2025. ACAT1-Mediated ME2 Acetylation Drives Chemoresistance in Ovarian Cancer by Linking Glutaminolysis to Lactate Production.. Adv Sci (Weinh) 12(14):e2416467 PMID: 39951294
- 4. Li G et al.. 2024. NAT10/ac4C/JunB facilitates TNBC malignant progression and immunosuppression by driving glycolysis addiction.. J Exp Clin Cancer Res 43(1):278 PMID: 39363363
- 5. Wei C et al.. 2025. Nuclear mitochondrial acetyl-CoA acetyltransferase 1 orchestrates natural killer cell-dependent antitumor immunity in colorectal cancer.. Signal Transduct Target Ther 10(1):138 PMID: 40289129
- 6. Zhu Y et al.. 2020. Dynamic Regulation of ME1 Phosphorylation and Acetylation Affects Lipid Metabolism and Colorectal Tumorigenesis.. Mol Cell 77(1):138-149.e5 PMID: 31735643
- 7. Li T et al.. 2025. Jianpi-Huogu Prescription Repairs Nontraumatic Osteonecrosis of the Femoral Head by Inhibiting NAMPT/STK11/HMGCR/ACAT1 Axis-Mediated Lipid Production.. J Cell Mol Med 29(18):e70858 PMID: 40988117
- 8. Huynh TN et al.. 2024. Inhibiting the Cholesterol Storage Enzyme ACAT1/SOAT1 in Aging Apolipoprotein E4 Mice Alters Their Brains' Inflammatory Profiles.. Int J Mol Sci 25(24) PMID: 39769453
