ArticleThe Journal of biological chemistry2016
Cell Autonomous and Nonautonomous Function of CUL4B in Mouse Spermatogenesis.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Integrative multi-omics reveals CUL4B as a modulator of macrophage pyroptosis and innate defense againstScience advances · 2026Article
- The intricate dance of RNA-binding proteins: unveiling the mechanisms behind male infertility.Human reproduction update · 2026Review
- GABA transporter 1 is a promising drug target for CUL4B mutation-associated epilepsy.Acta pharmacologica Sinica · 2025Article
- A novel CUL4B gene variant activating Wnt4/β-catenin signal pathway to karyotype 46, XY female with disorders of sex development.Biological research · 2025Article
- Proteostasis as a Sentry for Sperm Quality and Male Fertility.Advances in experimental medicine and biology · 2025Review
- DCUN1D2 is insignificant for spermatogenesis and male fertility in mice.American journal of translational research · 2025Article
- Cullin 4B-RING E3 ligase negatively regulates the immunosuppressive capacity of mesenchymal stem cells by suppressing iNOS.Cell death and differentiation · 2025Article
- 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
- Biomarker-based human and animal sperm phenotyping: the good, the bad and the ugly†.Biology of reproduction · 2024Review
- Article
- Zebrafish ambra1b knockout reveals a novel role for Ambra1 in primordial germ cells survival, sex differentiation and reproduction.Biological research · 2023Article
- Myocardial Infarction-Induced INSL6 Decrease Contributes to Breast Cancer Progression.Disease markers · 2023Article
- Ubiquitin ligases: guardians of mammalian development.Nature reviews. Molecular cell biology · 2022Review
- Review
- Proteolysis in Reproduction: Lessons From Gene-Modified Organism Studies.Frontiers in endocrinology · 2022Review
- Article
- DDB1- and CUL4-associated factor 8 plays a critical role in spermatogenesis.Frontiers of medicine · 2021Article
- Neddylation regulation of mitochondrial structure and functions.Cell & bioscience · 2021Review
- A genetic screen in Drosophila reveals an unexpected role for the KIP1 ubiquitination-promoting complex in male fertility.PLoS genetics · 2020Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
CUL4B ubiquitin ligase belongs to the cullin-RING ubiquitin ligase family. Although sharing many sequence and structural similarities, CUL4B plays distinct roles in spermatogenesis from its homologous protein CUL4A. We previously reported that genetic ablation ofCul4ain mice led to male infertility because of aberrant meiotic progression. In the present study, we generated Cul4bgerm cell-specific conditional knock-out (Cul4b(Vasa)),as well asCul4bglobal knock-out (Cul4b(Sox2)) mouse, to investigate its roles in spermatogenesis. Germ cell-specific deletion of Cul4bled to male infertility, despite normal testicular morphology and comparable numbers of spermatozoa. Notably, significantly impaired sperm mobility caused by reduced mitochondrial activity and glycolysis level were observed in the majority of the mutant spermatozoa, manifested by low, if any, sperm ATP production. Furthermore,Cul4b(Vasa)spermatozoa exhibited defective arrangement of axonemal microtubules and flagella outer dense fibers. Our mass spectrometry analysis identified INSL6 as a novel CUL4B substrate in male germ cells, evidenced by its direct polyubiquination and degradation by CUL4B E3 ligase. Nevertheless,Cul4bglobal knock-out males lost their germ cells in an age-dependent manner, implying failure of maintaining the spermatogonial stem cell niche in somatic cells. Taken together, our results show that CUL4B is indispensable to spermatogenesis, and it functions cell autonomously in male germ cells to ensure spermatozoa motility, whereas it functions non-cell-autonomously in somatic cells to maintain spermatogonial stemness. Thus, CUL4B links two distinct spermatogenetic processes to a single E3 ligase, highlighting the significance of ubiquitin modification during spermatogenesis.
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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.