ArticleCellular and molecular life sciences : CMLS2024
BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma.
Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 25 citations in OpenAlex.
- Low-Rank Variational Correction Estimation for Multi-Source Heterogeneous Quantile Linear Regression Models.Statistics in medicine · 2026Article
- Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.Molecular cancer · 2026Review
- SPOP-mediated K27-linked non-degradative ubiquitination of KCNN3 suppressing HCC progression via the CTCF-SATB1 axis.Cell death & disease · 2026Article
- Molecular insights for the tumor suppressor role of SPOP in prostate cancer.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Microglial NCAM1 attenuates ischemic brain injury by inhibiting NF-κB-driven neuroinflammation through IκBα stabilization.Journal of neuroinflammation · 2026Article
- Article
- BCLAF1 links RNA splicing to ATF4-dependent metabolic adaptation in acute myeloid leukemia.bioRxiv : the preprint server for biology · 2026Article
- PA28γ-containing tumor-derived exosomes promote T-cell dysfunction in head and neck squamous cell carcinoma.Cellular & molecular immunology · 2026Article
- Polysaccharides-gut microbiota interaction: mechanisms regulating the hepatocellular carcinoma immune microenvironment.Frontiers in immunology · 2026Review
- The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025Review
- Article
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- Post-translational modifications in hepatocellular carcinoma: mechanisms and therapeutic potential.Medical oncology (Northwood, London, England) · 2025Review
- Biochemical analysis of PD-L1 ubiquitination by CRL3Structure (London, England : 1993) · 2025Article
- Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies.Molecular cancer · 2025Review
- LMNB2-mediated high PD-L1 transcription triggers the immune escape of hepatocellular carcinoma.Cell death discovery · 2025Article
- Ubiquitination in hepatocellular carcinoma immunity.Journal of translational medicine · 2025Review
- Plasma protein levels and hepatocellular carcinoma: a Mendelian randomization study with drug screening implications.Discover oncology · 2025Article
- Challenges and opportunities for the diverse substrates of SPOP E3 ubiquitin ligase in cancer.Theranostics · 2025Review
- Integrating single-cell RNA sequencing with spatial transcriptomics reveal the fibrosis-related genes in hepatocellular carcinoma.Frontiers in immunology · 2025Article
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Authors and funding
21 authors at 1 institution in 1 country.
Funding
Abstract
Interaction between programmed death-1 (PD-1) ligand 1 (PD-L1) on tumor cells and PD-1 on T cells allows tumor cells to evade T cell-mediated immune surveillance. Strategies targeting PD-1/PD-L1 have shown clinical benefits in a variety of cancers. However, limited response rates in hepatocellular carcinoma (HCC) have prompted us to investigate the molecular regulation of PD-L1. Here, we identify B cell lymphoma-2-associated transcription factor 1 (BCLAF1) as a key PD-L1 regulator in HCC. Specifically, BCLAF1 interacts with SPOP, an E3 ligase that mediates the ubiquitination and degradation of PD-L1, thereby competitively inhibiting SPOP-PD-L1 interaction and subsequent ubiquitination and degradation of PD-L1. Furthermore, we determined an SPOP-binding consensus (SBC) motif mediating the BCLAF1-SPOP interaction on BCLAF1 protein and mutation of BCLAF1-SBC motif disrupts the regulation of the SPOP-PD-L1 axis. In addition, BCLAF1 expression was positively correlated with PD-L1 expression and negatively correlated with biomarkers of T cell activation, including CD3 and CD8, as well as with the level of immune cell infiltration in HCC tissues. Besides, BCLAF1 depletion leads to a significant reduction of PD-L1 expression in vitro, and this reduction of PD-L1 promoted T cell-mediated cytotoxicity. Notably, overexpression of BCLAF1 sensitized tumor cells to checkpoint therapy in an in vitro HCC cells-Jurkat cells co-culture model, whereas BCLAF1-SBC mutant decreased tumor cell sensitivity to checkpoint therapy, suggesting that BCLAF1 and its SBC motif serve as a novel therapeutic target for enhancing anti-tumor immunity in HCC.
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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.