ArticleMolecular & cellular proteomics : MCP2016
Nuclear Phosphoproteomic Screen Uncovers ACLY as Mediator of IL-2-induced Proliferation of CD4+ T lymphocytes.
Article in Molecular & cellular proteomics : MCP, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- The role of lipid metabolic reprogramming in tumor microenvironment.Theranostics · 2023Pooled it
- New insights into the ACLY-mediated metabolic and epigenetic interplay in macrophages.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Fatty acid metabolic reprogramming in the tumor microenvironment: Unraveling mechanisms and therapeutic prospects.Genes & diseases · 2026Review
- Dynamic Evolution of the Tumor Immune Microenvironment in Malignant Tumors and Emerging Therapeutic Paradigms.MedComm · 2025Review
- ACLY promotes NK cell effector function by regulating glycolysis and histone acetylation.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- A feedforward loop between ACLY and MYC supports T-ALL progression in vivo.Blood neoplasia · 2025Article
- ATP citrate lyase is an essential player in the metabolic rewiring induced by PTEN loss during T-ALL development.Blood advances · 2025Article
- Targeting dysregulated lipid metabolism in the tumor microenvironment.Archives of pharmacal research · 2023Review
- Targeted Quantification of Protein Phosphorylation and Its Contributions towards Mathematical Modeling of Signaling Pathways.Molecules (Basel, Switzerland) · 2023Review
- Metabolic reprogramming and epigenetic modifications on the path to cancer.Protein & cell · 2022Review
- ACLY and CKD: A Mendelian Randomization Analysis.Kidney international reports · 2022Article
- Metabolic regulation in the immune response to cancer.Cancer communications (London, England) · 2021Review
- Integrative computational approach identifies drug targets in CD4NPJ systems biology and applications · 2021Article
- Exploring the Role of ATP-Citrate Lyase in the Immune System.Frontiers in immunology · 2021Review
- Dynamic Phosphoproteomics Uncovers Signaling Pathways Modulated by Anti-oncogenic Sphingolipid Analogs.Molecular & cellular proteomics : MCP · 2019Article
- NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells.Oncology reports · 2019Article
- Signaling and Function of Interleukin-2 in T Lymphocytes.Annual review of immunology · 2018Review
- Acetyl-CoA promotes glioblastoma cell adhesion and migration through CaGenes & development · 2018Article
- Spatiotemporal Control of Acetyl-CoA Metabolism in Chromatin Regulation.Trends in biochemical sciences · 2018Review
- Mevalonate Metabolism in Cancer Stemness and Trained Immunity.Frontiers in oncology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anti-cancer immunotherapies commonly rely on the use of interleukin-2 (IL-2) to promote the expansion of T lymphocytes. IL-2- dependent proliferation is the culmination of a complex network of phosphorylation-driven signaling events that impact on gene transcription through mechanisms that are not clearly understood. To study the role of IL-2 in the regulation of nuclear protein function we have performed an unbiased mass spectrometry-based study of the nuclear phosphoproteome of resting and IL-2-treated CD4(+) T lymphocytes. We detected 8521distinct phosphosites including many that are not yet reported in curated phosphorylation databases. Although most phosphorylation sites remained unaffected upon IL-2 treatment, 391 sites corresponding to 288 gene products showed robust IL-2-dependent regulation. Importantly, we show that ATP-citrate lyase (ACLY) is a key phosphoprotein effector of IL-2-mediated T-cell responses. ACLY becomes phosphorylated on serine 455 in T lymphocytes upon IL-2-driven activation of AKT, and depletion or inactivation of ACLY compromises IL-2-promoted T-cell growth. Mechanistically, we demonstrate that ACLY is required for enhancing histone acetylation levels and inducing the expression of cell cycle regulating genes in response to IL-2. Thus, the metabolic enzyme ACLY emerges as a bridge between cytokine signaling and proliferation of T lymphocytes, and may be an attractive candidate target for the development of more efficient anti-cancer immunotherapies.
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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.