The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by targeting PTEN degradation
Cullin ring-finger ubiquitin ligase 4 (CRL4) has multiple functions in the maintenance of oocyte survival and meiotic cell cycle progression. DCAF13, a novel CRL4 adaptor, is essential for oocyte development. But the mechanisms by which CRL4-DCAF13 supports meiotic maturation remained unclear. In this study, we demonstrated that DCAF13 stimulates the meiotic resumption-coupled activation of protein synthesis in oocytes, partially by maintaining the activity of PI3K signaling pathway. CRL4-DCAF13 targets the polyubiquitination and degradation of PTEN, a lipid phosphatase that inhibits PI3K pathway as well as oocyte growth and maturation. Dcaf13 knockout in oocytes caused decreased CDK1 activity and impaired meiotic cell cycle progression and chromosome condensation defects. As a result, chromosomes fail to be aligned at the spindle equatorial plate, the spindle assembly checkpoint is activated, and most Dcaf13 null oocytes are arrested at the prometaphase I. The DCAF13-dependent PTEN degradation mechanism fits in as a missing link between CRL4 ubiquitin E3 ligase and PI3K pathway, both of which are crucial for translational activation during oocyte GV-MII transition.
KeywordsFemale germ cell Meiosis DDB1–CUL4-associated factor 13 Female fertility Ubiquitin E3 ligase PI3K signaling pathway
This study is funded by the National Key Research and Developmental Program of China (2017YFC1001100, 2017YFC1001500, 2016YFC1000600), National Natural Science Foundation of China (31528016, 31671558), and The Key Research and Development Program of Zhejiang Province (2017C03022).
Compliance with ethical standards
Conflict of interest
The authors declare no competing interest.
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