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c-Cbl Acts as an E3 Ligase Against DDA3 for Spindle Dynamics and Centriole Duplication during Mitosis

Molecules and Cells 2019년 42권 12호 p.840 ~ 849
 ( Gwon Da-Som ) - Sookmyung Women’s University College of Pharmacy

 ( Hong Ji-Hee ) - Sookmyung Women’s University College of Pharmacy
 ( Jang Chang-Young ) - Sookmyung Women’s University College of Pharmacy

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.

키워드

c-Cbl; centriole; centrosome; DDA3; E3 ligase; spindle dynamics
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