ArticleNucleic acids research2015
DNA damage-induced activation of CUL4B targets HUWE1 for proteasomal degradation.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- mCell death and differentiation · 2026Article
- Ubiquitination degradation of GATA4 by CUL4B promotes ovarian cancer metastasis by inducing lysosomal acidification.Genome biology · 2026Article
- DEPTOR suppresses lymphomagenesis by promoting EGFR degradation via HUWE1 E3 ligase.Cell death and differentiation · 2025Article
- Restriction of influenza A virus replication by host DCAF7-CRL4B axis.Journal of virology · 2025Article
- Pan-Cancer Analysis of Homologous Recombination Deficiency in Cell Lines.Cancer research communications · 2024Article
- Dynamic role of CUL4B in radiation-induced intestinal injury-regeneration.Scientific reports · 2024Article
- Miz1 represses type I interferon production and limits viral clearance during influenza A virus infection.Science signaling · 2024Article
- CRL4b Inhibition Ameliorates Experimental Autoimmune Encephalomyelitis Progression.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Article
- Activating STING/TBK1 suppresses tumor growth via degrading HPV16/18 E7 oncoproteins in cervical cancer.Cell death and differentiation · 2024Article
- Biological insights in non-small cell lung cancer.Cancer biology & medicine · 2023Review
- Miz1 promotes KRAS-driven lung tumorigenesis by repressing the protocadherin Pcdh10.Cancer letters · 2023Article
- The giant E3 ligase HUWE1 is linked to tumorigenesis, spermatogenesis, intellectual disability, and inflammatory diseases.Frontiers in cellular and infection microbiology · 2022Review
- The E3 ubiquitin ligase Cul4b promotes CD4+ T cell expansion by aiding the repair of damaged DNA.PLoS biology · 2021Article
- CUL4B Promotes Temozolomide Resistance in Gliomas by Epigenetically RepressingFrontiers in oncology · 2021Article
- HUWE1 mediates inflammasome activation and promotes host defense against bacterial infection.The Journal of clinical investigation · 2020Article
- CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma.Cancer biology & medicine · 2020Article
- Quantitative proteomic and phosphoproteomic profiling of ischemic myocardial stunning in swine.American journal of physiology. Heart and circulatory physiology · 2020Article
- Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network.Nature communications · 2019Article
- Comparative proteomic analysis of Tibetan pig spermatozoa at high and low altitudes.BMC genomics · 2019Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The E3 ubiquitin ligase HUWE1/Mule/ARF-BP1 plays an important role in integrating/coordinating diverse cellular processes such as DNA damage repair and apoptosis. A previous study has shown that HUWE1 is required for the early step of DNA damage-induced apoptosis, by targeting MCL-1 for proteasomal degradation. However, HUWE1 is subsequently inactivated, promoting cell survival and the subsequent DNA damage repair process. The mechanism underlying its regulation during this process remains largely undefined. Here, we show that the Cullin4B-RING E3 ligase (CRL4B) is required for proteasomal degradation of HUWE1 in response to DNA damage. CUL4B is activated in a NEDD8-dependent manner, and ubiquitinates HUWE1 in vitro and in vivo. The depletion of CUL4B stabilizes HUWE1, which in turn accelerates the degradation of MCL-1, leading to increased induction of apoptosis. Accordingly, cells deficient in CUL4B showed increased sensitivity to DNA damage reagents. More importantly, upon CUL4B depletion, these phenotypes can be rescued through simultaneous depletion of HUWE1, consistent with the role of CUL4B in regulating HUWE1. Collectively, these results identify CRL4B as an essential E3 ligase in targeting the proteasomal degradation of HUWE1 in response to DNA damage, and provide a potential strategy for cancer therapy by targeting HUWE1 and the CUL4B E3 ligase.
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