Lats2 is an essential mitotic regulator required for the coordination of cell division
Norikazu Yabuta1, Nobuhiro Okada, Akihiko Ito
1Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka 565-0871, Japan.
Abstract:
Tumor suppressor Lats2 is a member of the conserved Dbf2 kinase family. It localizes to the centrosome and has been implicated in regulation of the cell cycle and apoptosis. However, the in vivo function of this kinase remains unclear. Here, we show that complete disruption of the gene encoding Lats2 in mice causes developmental defects in the nervous system and embryonic lethality. Furthermore, mutant cells derived from total LATS2-knock-out embryos exhibit mitotic defects including centrosome fragmentation and cytokinesis defects, followed by nuclear enlargement and multinucleation. We show that the Mob1 family, a regulator of mitotic exit, associates with Lats2 to induce its activation. We also show that the complete LATS2-knock-out cells exhibit an acceleration of exit from mitosis and marked down-regulation of critical mitotic regulators. These results suggest that Lats2 plays an essential mitotic role in coordinating accurate cytokinesis completion, governing the stabilization of other mitotic regulators.
Insights
Tumor suppressor Lats2 is crucial for embryonic development and cell division. Complete LATS2 gene disruption in mice leads to severe mitotic defects and embryonic lethality, highlighting its essential role in cell cycle regulation.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The tumor suppressor Lats2 (Large tumor suppressor 2) is a kinase involved in cell cycle regulation and apoptosis.
- Its precise in vivo function, particularly during mitosis, remains largely uncharacterized.
Purpose of the Study:
- To elucidate the in vivo function of the Lats2 kinase.
- To investigate the consequences of Lats2 deficiency on cell cycle progression and mitotic fidelity.
Main Methods:
- Generation and analysis of LATS2-knock-out mice.
- Characterization of mitotic defects in LATS2-deficient cells.
- Investigation of Lats2 interaction with Mob1 and its role in mitotic exit.
Main Results:
- Complete LATS2 gene disruption in mice results in developmental defects, particularly in the nervous system, and embryonic lethality.
- LATS2-knock-out cells display significant mitotic abnormalities, including centrosome fragmentation, cytokinesis failure, nuclear enlargement, and multinucleation.
- Lats2 interacts with Mob1, leading to its activation and influencing mitotic exit.
- LATS2-deficient cells show accelerated exit from mitosis and downregulation of key mitotic regulators.
Conclusions:
- Lats2 plays a critical role in ensuring accurate cytokinesis completion during mitosis.
- Lats2 is essential for stabilizing mitotic regulators, thereby maintaining genomic integrity.
- Dysregulation of Lats2 function contributes to developmental abnormalities and potentially tumorigenesis.
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