ArticleScientific reports2016
Human X-linked Intellectual Disability Factor CUL4B Is Required for Post-meiotic Sperm Development and Male Fertility.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 34 citations in OpenAlex.
- Integrative multi-omics reveals CUL4B as a modulator of macrophage pyroptosis and innate defense againstScience advances · 2026Article
- Neddylation is indispensable for early meiotic progression in spermatocytes via destabilizing HORMAD1 by SCF ubiquitin E3 ligase during synapsis.Cell & bioscience · 2026Article
- The Potential Role of Deubiquitinating Enzymes (DUBs) in Male Fertility.Biomolecules · 2026Review
- GABA transporter 1 is a promising drug target for CUL4B mutation-associated epilepsy.Acta pharmacologica Sinica · 2025Article
- Cullin 4B-RING E3 ligase negatively regulates the immunosuppressive capacity of mesenchymal stem cells by suppressing iNOS.Cell death and differentiation · 2025Article
- In silico exploring of the epigenetic factors in teratozoospermia: A focus onMolecular biology research communications · 2025Article
- The Role of Ubiquitin-Proteasome System (UPS) in Asthma Pathology.Journal of asthma and allergy · 2025Review
- CUL4B protects kidneys from acute injury by restraining p53/PAI-1 signaling.Cell death & disease · 2024Article
- The X-linked intellectual disability gene CUL4B is critical for memory and synaptic function.Acta neuropathologica communications · 2024Article
- Article
- CRL4B complex-mediated H2AK119 monoubiquitination restrains Th1 and Th2 cell differentiation.Cell death and differentiation · 2023Article
- Large-scale analyses of the X chromosome in 2,354 infertile men discover recurrently affected genes associated with spermatogenic failure.American journal of human genetics · 2022Article
- Ubiquitin ligases: guardians of mammalian development.Nature reviews. Molecular cell biology · 2022Review
- Proteolysis in Reproduction: Lessons From Gene-Modified Organism Studies.Frontiers in endocrinology · 2022Review
- CUL4The American journal of pathology · 2021Article
- DDB1- and CUL4-associated factor 8 plays a critical role in spermatogenesis.Frontiers of medicine · 2021Article
- Embryonic Cul4b is important for epiblast growth and location of primitive streak layer cells.PloS one · 2019Article
- Deletion of DDB1- and CUL4- associated factor-17 (Dcaf17) gene causes spermatogenesis defects and male infertility in mice.Scientific reports · 2018Article
- Nuclear organization during in vitro differentiation of porcine mesenchymal stem cells (MSCs) into adipocytes.Histochemistry and cell biology · 2018Article
- Functional analysis of Cullin 3 E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2018Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we demonstrate that an E3-ubiquitin ligase associated with human X-linked intellectual disability, CUL4B, plays a crucial role in post-meiotic sperm development. Initially, Cul4b(Δ)/Y male mice were found to be sterile and exhibited a progressive loss in germ cells, thereby leading to oligoasthenospermia. Adult Cul4b mutant epididymides also contained very low numbers of mature spermatozoa, and these spermatazoa exhibited pronounced morphological abnormalities. In post-meiotic spermatids, CUL4B was dynamically expressed and mitosis of spermatogonia and meiosis of spermatocytes both appeared unaffected. However, the spermatids exhibited significantly higher levels of apoptosis during spermiogenesis, particularly during the acrosome phase through the cap phase. Comparative proteomic analyses identified a large-scale shift between wild-type and Cul4b mutant testes during early post-meiotic sperm development. Ultrastructural pathology studies further detected aberrant acrosomes in spermatids and nuclear morphology. The protein levels of both canonical and non-canonical histones were also affected in an early spermatid stage in the absence of Cul4b. Thus, X-linked CUL4B appears to play a critical role in acrosomal formation, nuclear condensation, and in regulating histone dynamics during haploid male germ cell differentiation in relation to male fertility in mice. Thus, it is possible that CUL4B-selective substrates are required for post-meiotic sperm morphogenesis.
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