ArticleNature communications2024
Cullin-5 deficiency promotes chimeric antigen receptor T cell effector functions potentially via the modulation of JAK/STAT signaling pathway.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- ABTB1, as an E3 ubiquitin ligase, suppresses Th17 cell differentiation and mitigates autoimmune inflammation by promoting STAT3 ubiquitination and degradation.Cellular & molecular immunology · 2026Article
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Genome-wide CRISPR screens in primary human natural killer cells identify countermeasures against immunosuppressive environment.Nature communications · 2026Article
- CUL5 E3 ubiquitin ligase regulates the evasion of bladder cancer cells to CD8+ T cell-mediated killing by inhibiting autophagy.PLoS biology · 2026Article
- CENPM as a biomarker and therapeutic target for lymph node metastasis in thyroid carcinoma.Frontiers in genetics · 2026Article
- Cul5: immune cell function and therapeutic potential.Frontiers in immunology · 2026Review
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- Improving CAR T cell therapy against malignancies through gene knock-down/out strategies: a systematic review.Cancer cell international · 2025Review
- Cytokine Engineering in CAR-T Cell Therapy: Next-Generation Strategies.Immune network · 2025Review
- In vivo CAR-T cell engineering: concept, research progress, potential challenges and enhancement strategies.Experimental hematology & oncology · 2025Review
- From intracellular drivers to immune modulators: emerging paradigms in oncogenic pathway-directed immunotherapy optimization.Cell communication and signaling : CCS · 2025Review
- In vivo genome-wide CRISPR screens in human T cells to enhance T cell therapy for solid tumors.bioRxiv : the preprint server for biology · 2025Article
- The role of ubiquitin ligases in regulating immune cell functions.Frontiers in immunology · 2025Review
- The mFrontiers in oncology · 2025Article
- Transcriptome analysis of nitrogen assimilation preferences inFrontiers in microbiology · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR) T cell is a promising therapy for cancer, but factors that enhance the efficacy of CAR T cell remain elusive. Here we perform a genome-wide CRISPR screening to probe genes that regulate the proliferation and survival of CAR T cells following repetitive antigen stimulations. We find that genetic ablation of CUL5, encoding a core element of the multi-protein E3 ubiquitin-protein ligase complex, cullin-RING ligase 5, enhances human CD19 CAR T cell expansion potential and effector functions, potentially via the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. In this regard, CUL5 knockout CD19 CAR T cells show sustained STAT3 and STAT5 phosphorylation, as well as delayed phosphorylation and degradation of JAK1 and JAK3. In vivo, shRNA-mediated knockdown of CUL5 enhances CD19 CAR T treatment outcomes in tumor-bearing mice. Our findings thus imply that targeting CUL5 in the ubiquitin system may enhance CAR T cell effector functions to enhance immunotherapy efficacy.
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