2. Academic Validation
  3. FBXO47 regulates centromere pairing as key component of centromeric SCF E3 ligase in mouse spermatocytes

FBXO47 regulates centromere pairing as key component of centromeric SCF E3 ligase in mouse spermatocytes

  • Commun Biol. 2024 Sep 7;7(1):1099. doi: 10.1038/s42003-024-06782-6.
Ani Ma # 1 2,  Yali Yang # 3,  Lianbao Cao 4,  Lijun Chen 5,  Jian V Zhang 6 7 8
Affiliations

Affiliations

  • 1 Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China. maani0431@126.com.
  • 2 Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China. maani0431@126.com.
  • 3 Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
  • 4 Department of Gynecological Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • 5 Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China.
  • 6 Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China. jian.zhang@siat.ac.cn.
  • 7 Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen, Guangdong, China. jian.zhang@siat.ac.cn.
  • 8 Sino-European Center of Biomedicine and Health, Shenzhen, Guangdong, China. jian.zhang@siat.ac.cn.
  • # Contributed equally.
PMID: 39244596 DOI: 10.1038/s42003-024-06782-6
Abstract

Centromere pairing is crucial for synapsis in meiosis. This study delves into the Skp1-Cullin1-F-box protein (SCF) E3 ubiquitin Ligase complex, specifically focusing on F-box protein 47 (FBXO47), in mouse meiosis. Here, we revealed that FBXO47 is localized at the centromere and it regulates centromere pairing cooperatively with SKP1 to ensure proper synapsis in pachynema. The absence of FBXO47 causes defective centromeres, resulting in incomplete centromere pairing, which leads to corruption of SC at centromeric ends and along chromosome axes, triggering premature dissociation of chromosomes and pachytene arrest. FBXO47 deficient pachytene spermatocytes exhibited drastically reduced SKP1 expression at centromeres and chromosomes. Additionally, FBXO47 stabilizes SKP1 by down-regulating its ubiquitination in HEK293T cells. In essence, we propose that FBXO47 collaborates with SKP1 to facilitate centromeric SCF formation in spermatocytes. In summary, we posit that the centromeric SCF E3 Ligase complex regulates centromere pairing for pachynema progression in mice.

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