BMB Reports 2017; 50(7): 379-383
Repression of the F-box protein Skp2 is essential for actin damage-induced tetraploid G1 arrest

Yongsam Jo & Deug Y. Shin*

Department of Microbiology, Dankook University College of Medicine, Cheonan 31116, Korea
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Received: April 14, 2017; Revised: May 12, 2017; Accepted: June 14, 2017; Published online: July 31, 2017.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

We previously reported that p53 plays a role as a key regulator in the tetraploid G1 checkpoint, which is activated by actin damage-induced cytokinesis blockade and then prevents uncoupled DNA replication and nuclear division without cytokinesis. In this study, we investigated a role of Skp2, which targets CDK2 inhibitor p27/Kip1, in actin damage-induced tetraploid G1 arrest. Expression of Skp2 was reduced, but p27/Kip1 was increased, after actin damage-induced cytokinesis blockade. The role of Skp2 repression in tetraploid G1 arrest was investigated by analyzing the effects of ectopic expression of Skp2. After actin damage, ectopic expression of Skp2 resulted in DNA synthesis and accumulation of multinucleated cells, and ultimately, induction of apoptosis. These results suggest that Skp2 repression is important for sustaining tetraploid G1 arrest after cytokinesis blockade and is required to prevent uncoupled DNA replication and nuclear division without cytokinesis.
Keywords: Actin damage, Cytokinesis, Pectenotoxin-2, Skp2, Tetraploid G1 arrest

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