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CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation
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SYSNO ASEP 0544148 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation Author(s) Liďák, Tomáš (UMG-J)
Baloghová, Nikol (UMG-J)
Kořínek, Vladimír (UMG-J) RID
Sedláček, Radislav (UMG-J) RID
Balounová, Jana (UMG-J)
Kašpárek, Petr (UMG-J)
Čermák, Lukáš (UMG-J) ORCIDNumber of authors 7 Article number 5394 Source Title International Journal of Molecular Sciences. - : MDPI
Roč. 22, č. 10 (2021)Number of pages 25 s. Publication form Online - E Language eng - English Country CH - Switzerland Keywords dcaf12 ; wdr40a ; mov10 ; C-terminal degron ; spermatogenesis ; T cell activation Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology R&D Projects GA18-27408S GA ČR - Czech Science Foundation (CSF) LM2018126 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMG-J - RVO:68378050 UT WOS 000661988100001 DOI 10.3390/ijms22105394 Annotation 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 gamma-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. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2022 Electronic address https://www.mdpi.com/1422-0067/22/10/5394
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