ArticleNature communications2021
PD-L1 degradation is regulated by electrostatic membrane association of its cytoplasmic domain.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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Who cites it
42 citing papers in PubMed, 75 citations in OpenAlex.
- LAG3 checkpoint function and its mechanism of action in therapeutic targeting.Nature reviews. Immunology · 2026Review
- A conserved basic motif mediates membrane anchoring and TRAF2 recruitment across costimulatory TNFRs.The EMBO journal · 2026Article
- Role of the Proteasome System in Shaping Cellular Immunological Characteristics and Its Impact in Modulating the Pathogenesis of Immune-Related Diseases.Cells, tissues, organs · 2026Review
- Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma.Molecular oncology · 2026Article
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- Interferon-gamma-inducible protein 30 prevents IFN-γ-receptor 1 degradation to maintain PD-L1 and MHC-II levels in metastatic melanoma.Cell communication and signaling : CCS · 2026Article
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- The lipid-metabolic enzyme HSD17B12 drives lysosomal degradation of PD-L1 potentiating anti-tumor immunity in a mouse model.PLoS biology · 2026Article
- Intracellular PD-L1: Functions, Regulation, and Therapeutic Implications.International journal of biological sciences · 2026Review
- Biochemical analysis of PD-L1 ubiquitination by CRL3Structure (London, England : 1993) · 2025Article
- Tumor Membrane Based Delivery System Encapsulating Metfornin and TPP1 Peptide for Tumor Immune Therapy.ACS biomaterials science & engineering · 2025Article
- Review
- Immunomodulating platelet-mimicking nanoparticles for AIE-based enhanced photodynamic immunotherapy against lung cancer.Materials today. Bio · 2025Article
- Charge-based immunoreceptor signalling in health and disease.Nature reviews. Immunology · 2025Review
- PD-L1-CD80 interactions are required for intracellular signaling necessary for dendritic cell migration.Science advances · 2025Article
- Atherosclerosis and the Bidirectional Relationship Between Cancer and Cardiovascular Disease: From Bench to Bedside, Part 2 Management.International journal of molecular sciences · 2025Review
- Intrinsic PD-L1 Degradation Induced by a Novel Self-Assembling Hexapeptide for Enhanced Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PD-1 is conserved from sharks to humans: new insights into PD-1, PD-L1, PD-L2, and SHP-2 evolution.Frontiers in immunology · 2025Article
- Fatty acid synthase (FASN) is a tumor-cell-intrinsic metabolic checkpoint restricting T-cell immunity.Cell death discovery · 2024Article
- Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The cytoplasmic domain of PD-L1 (PD-L1-CD) regulates PD-L1 degradation and stability through various mechanism, making it an attractive target for blocking PD-L1-related cancer signaling. Here, by using NMR and biochemical techniques we find that the membrane association of PD-L1-CD is mediated by electrostatic interactions between acidic phospholipids and basic residues in the N-terminal region. The absence of the acidic phospholipids and replacement of the basic residues with acidic residues abolish the membrane association. Moreover, the basic-to-acidic mutations also decrease the cellular abundance of PD-L1, implicating that the electrostatic interaction with the plasma membrane mediates the cellular levels of PD-L1. Interestingly, distinct from its reported function as an activator of AMPK in tumor cells, the type 2 diabetes drug metformin enhances the membrane dissociation of PD-L1-CD by disrupting the electrostatic interaction, thereby decreasing the cellular abundance of PD-L1. Collectively, our study reveals an unusual regulatory mechanism that controls the PD-L1 level in tumor cells, suggesting an alternative strategy to improve the efficacy of PD-L1-related 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.