Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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c-Cbl Acts as an E3 Ligase Against DDA3 for Spindle Dynamics and Centriole Duplication during Mitosis

  • Gwon, Dasom (Drug Information Research Institute, College of Pharmacy, Sookmyung Women's University) ;
  • Hong, Jihee (Drug Information Research Institute, College of Pharmacy, Sookmyung Women's University) ;
  • Jang, Chang-Young (Drug Information Research Institute, College of Pharmacy, Sookmyung Women's University)
  • Received : 2019.06.28
  • Accepted : 2019.09.30
  • Published : 2019.12.31
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Abstract

The spatiotemporal mitotic processes are controlled qualitatively by phosphorylation and qualitatively by ubiquitination. Although the SKP1-CUL1-F-box protein (SCF) complex and the anaphase-promoting complex/cyclosome (APC/C) mainly mediate ubiquitin-dependent proteolysis of mitotic regulators, the E3 ligase for a large portion of mitotic proteins has yet to be identified. Here, we report c-Cbl as an E3 ligase that degrades DDA3, a protein involved in spindle dynamics. Depletion of c-Cbl led to increased DDA3 protein levels, resulting in increased recruitment of Kif2a to the mitotic spindle, a concomitant reduction in spindle formation, and chromosome alignment defects. Furthermore, c-Cbl depletion induced centrosome over-duplication and centriole amplification. Therefore, we concluded that c-Cbl controls spindle dynamics and centriole duplication through its E3 ligase activity against DDA3.

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References

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