A Cul3-based E3 ligase regulates mitosis and is required to maintain the spindle assembly checkpoint in human cells.
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.
Sumara
Izabela
I
Institute of Biochemistry, ETH Zurich, Zurich, Switzerland. izabela.sumara@bc.biol
Peter
Matthias
M
D064107:Aurora Kinase B; D064127:Aurora Kinases; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology*; D020090:Chromosome Segregation / Q000502:physiology; D044842:Cullin Proteins / Q000502:physiology*; D006801:Humans; D018386:Kinetochores / Q000502:physiology; D008938:Mitosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D054875:Ubiquitination
C503645:CUL3 protein, human; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; D044767:Ubiquitin-Protein Ligases; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases