ArticleGenes & development2016
Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 148 citations in OpenAlex.
- New insights into the ACLY-mediated metabolic and epigenetic interplay in macrophages.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Lipid Metabolic Reprogramming in Lung Cancer: Mechanisms and Therapeutic Targets in the Tumor Microenvironment.International journal of cancer · 2026Review
- GSTM4 Suppresses Prostate Cancer Progression by Targeting TRIM27-mediated ACLY Ubiquitination and Lipid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- De Novo Lipogenesis in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Fatty acid metabolic reprogramming in the tumor microenvironment: Unraveling mechanisms and therapeutic prospects.Genes & diseases · 2026Review
- The hidden players: LncRNA-Encoded micropeptides in cancer hallmarks.Cellular and molecular life sciences : CMLS · 2026Review
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- SLC7A5-ERBB2 axis drives olaparib resistance via de novo lipid synthesis in ovarian cancer.Oncogene · 2026Article
- Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.Cancer medicine · 2025Review
- Membrane-associated ring-CH-type finger 2 protects against metabolic dysfunction-associated fatty liver disease by targeting fatty acid synthase.Molecular metabolism · 2025Article
- Identifying Genes Associated with the Anticancer Activity of a Fluorinated Chalcone in Triple-Negative Breast Cancer Cells Using Bioinformatics Tools.International journal of molecular sciences · 2025Article
- KLHL25-ACLY module functions as a switch in the fate determination of the differentiation of iTreg/Th17.Communications biology · 2025Article
- Acetyl-CoA synthesis in the skin is a key determinant of systemic lipid homeostasis.Cell reports · 2025Article
- Identification and Validation of Lipid Metabolism Gene FASN-Associated miRNA in Wilms Tumor.Biochemical genetics · 2025Article
- Dehydrocostus lactone suppresses gastric cancer progression by targeting ACLY to inhibit fatty acid synthesis and autophagic flux.Journal of advanced research · 2025Article
- Ubiquitination in lipid metabolism reprogramming: implications for pediatric solid tumors.Frontiers in immunology · 2025Review
- The role of ubiquitination and deubiquitination in cancer lipid metabolism.Frontiers in oncology · 2025Review
- Role of ATP citrate lyase and its complementary partner on fatty acid synthesis in gastric cancer.Scientific reports · 2024Article
- Roles of posttranslational modifications in lipid metabolism and cancer progression.Biomarker research · 2024Review
- Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Increased lipid synthesis is a key characteristic of many cancers that is critical for cancer progression. ATP-citrate lyase (ACLY), a key enzyme for lipid synthesis, is frequently overexpressed or activated in cancer to promote lipid synthesis and tumor progression. Cullin3 (CUL3), a core protein for the CUL3-RING ubiquitin ligase complex, has been reported to be a tumor suppressor and frequently down-regulated in lung cancer. Here, we found that CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells. Through negative regulation of ACLY, CUL3 inhibits lipid synthesis, cell proliferation, and xenograft tumor growth of lung cancer cells. Furthermore, ACLY inhibitor SB-204990 greatly abolishes the promoting effect of CUL3 down-regulation on lipid synthesis, cell proliferation, and tumor growth. Importantly, low CUL3 expression is associated with high ACLY expression and poor prognosis in human lung cancer. In summary, our results identify CUL3-KLHL25 ubiquitin ligase as a novel negative regulator for ACLY and lipid synthesis and demonstrate that decreased CUL3 expression is an important mechanism for increased ACLY expression and lipid synthesis in lung cancer. These results also reveal that negative regulation of ACLY and lipid synthesis is a novel and critical mechanism for CUL3 in tumor suppression.
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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 OpenQuestion graph.