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A Cul3-Based E3 Ligase Regulates Mitosis and is Required to Maintain the Spindle Assembly Checkpoint in Human Cells

Volume 6, Issue 24   December 15, 2007
Pages 3004 - 3010
http://dx.doi.org/10.4161/cc.6.24.5068
Authors: Izabela Sumara and Matthias Peter

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Abstract:
The spindle assembly checkpoint (SAC) is a mechanism that prevents premature chromosome segregation in anaphase before all chromosomes are correctly attached to the mitotic spindle. Errors in chromosome segregation lead to aneuploidy, which may be causally involved in tumorgenesis. Kinetochore complexes are the structural components of the SAC, which are tightly regulated by various mechanisms including phosphorylation and ubiquitin-dependent proteolysis. Recent studies shed new light on the regulatory pathways of the ubiquitin proteasome system involved in SAC signaling. Here we present evidence that a Cul3-based E3 ubiquitin-ligase is required to maintain SAC signaling in human cells. Inactivation of the Cul3/KLHL9/KLHL13 ligase leads to premature degradation of Cyclin B and exit from the mitotic state in the presence of microtubule poisons. We discuss possible mechanisms how Cul3 may be required to maintain SAC activity by ubiquitination of the chromosomal passenger protein Aurora B.

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