ArticlePLoS biology2021
The E3 ubiquitin ligase Cul4b promotes CD4+ T cell expansion by aiding the repair of damaged DNA.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Editorial: Ubiquitination in tumor pathogenesis and progression and its therapeutic potential.Frontiers in immunology · 2026Article
- Elucidating the immunomodulatory roles and mechanisms of CUL4B in the immune system: a comprehensive review.Frontiers in immunology · 2025Review
- CRL4b Inhibition Ameliorates Experimental Autoimmune Encephalomyelitis Progression.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- IGFBP3 induces PD-L1 expression to promote glioblastoma immune evasion.Cancer cell international · 2024Article
- The Cullin-RING Ligase Family in Immune Regulation.Advances in experimental medicine and biology · 2024Review
- B cell expression of E3 ubiquitin ligase Cul4b promotes chronic gammaherpesvirus infectionJournal of virology · 2023Article
- c-Myc uses Cul4b to preserve genome integrity and promote antiviral CD8Nature communications · 2023Article
- Cullin 4B-RING E3 ligase complex in immune cell differentiation and function.Cellular & molecular immunology · 2023Article
- CRL4B complex-mediated H2AK119 monoubiquitination restrains Th1 and Th2 cell differentiation.Cell death and differentiation · 2023Article
- Effects of SMC1A on immune microenvironment and cancer stem cells in colon adenocarcinoma.Cancer medicine · 2023Article
- Neddylation Regulation of Immune Responses.Research (Washington, D.C.) · 2023Review
- Machine learning-based neddylation landscape indicates different prognosis and immune microenvironment in endometrial cancer.Frontiers in oncology · 2023Article
- The ubiquitin ligase Cul5 regulates CD4Nature communications · 2022Article
- CUL4B is a Potential Novel Prognostic Biomarker and is Correlated with Immune Infiltrates in Malignant Pleural Mesothelioma.International journal of general medicine · 2022Article
- Association Between Neddylation and Immune Response.Frontiers in cell and developmental biology · 2022Review
- Ddb1 Is Essential for the Expansion of CD4Frontiers in immunology · 2021Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The capacity for T cells to become activated and clonally expand during pathogen invasion is pivotal for protective immunity. Our understanding of how T cell receptor (TCR) signaling prepares cells for this rapid expansion remains limited. Here we provide evidence that the E3 ubiquitin ligase Cullin-4b (Cul4b) regulates this process. The abundance of total and neddylated Cul4b increased following TCR stimulation. Disruption of Cul4b resulted in impaired proliferation and survival of activated T cells. Additionally, Cul4b-deficient CD4+ T cells accumulated DNA damage. In T cells, Cul4b preferentially associated with the substrate receptor DCAF1, and Cul4b and DCAF1 were found to interact with proteins that promote the sensing or repair of damaged DNA. While Cul4b-deficient CD4+ T cells showed evidence of DNA damage sensing, downstream phosphorylation of SMC1A did not occur. These findings reveal an essential role for Cul4b in promoting the repair of damaged DNA to allow survival and expansion of activated T cells.
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