Multisubunit cullin-RING ubiquitin ligase 4 (CRL4)-DCAF12 recognizes the C-terminal degron containing acidic amino acid residues. However, its physiological roles and substrates are largely unknown. Purification of CRL4-DCAF12 complexes revealed a wide range of potential substrates, including MOV10, an "ancient" RNA-induced silencing complex (RISC) complex RNA helicase. We show that DCAF12 controls the MOV10 protein level via its C-terminal motif in a proteasome- and CRL-dependent manner. Next, we generated Dcaf12 knockout mice and demonstrated that the DCAF12-mediated degradation of MOV10 is conserved in mice and humans. Detailed analysis of Dcaf12-deficient mice revealed that their testes produce fewer mature sperms, phenotype accompanied by elevated MOV10 and imbalance in meiotic markers SCP3 and γ-H2AX. Additionally, the percentages of splenic CD4+ T and natural killer T (NKT) cell populations were significantly altered. In vitro, activated Dcaf12-deficient T cells displayed inappropriately stabilized MOV10 and increased levels of activated caspases. In summary, we identified MOV10 as a novel substrate of CRL4-DCAF12 and demonstrated the biological relevance of the DCAF12-MOV10 pathway in spermatogenesis and T cell activation.

• MeSH
• Lymphocyte Activation physiology   MeSH
• Antigens, Neoplasm metabolism   MeSH
• Cell Line MeSH
• CD4-Positive T-Lymphocytes metabolism   MeSH
• HCT116 Cells MeSH
• HEK293 Cells MeSH
• HeLa Cells MeSH
• Humans MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Cell Line, Tumor MeSH
• Natural Killer T-Cells metabolism   MeSH
• Proteasome Endopeptidase Complex metabolism   MeSH
• RNA Helicases metabolism   MeSH
• Spermatogenesis physiology   MeSH
• Ubiquitin metabolism   MeSH
• Ubiquitin-Protein Ligases metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH