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Mol Cells. 2019 Nov 14. doi: 10.14348/molcells.2019.0142. [Epub ahead of print]

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

Author information

1
Drug Information Research Institute, College of Pharmacy, Sookmyung Women's University, Seoul 04310, Korea.
2
These authors contributed equally to this work.

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.

KEYWORDS:

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

PMID:
31722512
DOI:
10.14348/molcells.2019.0142
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