Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery (Nature, 2008, 455:119-123)

報告日期: 2008/12/02
報告時間: 17:05/17:55
報告學生: 李育誠
講評老師: 洪良宜
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971202-3.pdf

Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery

Nature, 2008, 455: 119-124

 

Speaker: 李育誠

Commentator: 洪良宜老師

Time: 2008/12/02 17:05-17:55

Room: 602

 

Abstract

 

The G2/M transition of cell cycle is regulated by the cyclin B/cdk1 kinase complex. During the G2 phase, inactive cyclin B/cdk1 complex accumulates in cells due to inhibitory phosphorylation of cdk1 on Thr14 and Tyr15 by the Wee1 and Myt1 kinases. During mitotic onset, PLK1 is implicated in several processes that contribute to the activation of cyclin B/cdk1. Briefly, PLK1 directly phosphorylates Wee1, Myt1, cyclin B and Cdc25 phosphatase result in Wee1 and Myt1 protein degradation, dephosphorylation Thr14 and Tyr15 of cdk1 by cdc25 and nuclear translocation of cyclin B/cdk1 complex to promote mitotic entry. However, when cells encounter to DNA damage, the G2 DNA damage checkpoint prevents mitotic entry. Activation of checkpoint kinases ATM, ATR, Chk1 and Chk2 mediate nuclear exclusion of Cdc25 and degradation, activation of Wee1 and inhibit PLK1 activity to arrest cell cycle progression and turn on the DNA repair mechanisms that serve to protect the cell genomic integrity and prevent cell transformation. Once DNA damage is repaired, the DNA damage checkpoint is silenced so that cell cycle progression is allowed to re-start (the process is defined as checkpoint recovery). Previously study showed that PLK1 is required for checkpoint recovery after a G2 DNA damage arrest but which kinase is responsible for PLK1 activation remains unclear, therefore the authors use the process of checkpoint recovery to study when and how PLK1 is activated. In the study, they use caffeine to inhibit checkpoint kinases-ATM/ATR lead to switch off checkpoint and allow cells to perform “checkpoint recovery” after DNA damage. In this study they find that during the caffeine-induced checkpoint recovery after DNA damage, aurora A kinase, together with the cofactor-Bora can phosphorylate PLK1 at T210 and enhance PLK1 kinase activity in G2 phase. The PLK1 kinase activity is required for checkpoint recovery to promote mitotic entry.  

 

Reference:

1.   Polo-like Kinase-1 Controls Recovery from a G2 DNA Damage-Induced Arrest in Mammalian Cells Molecular Cell 2004:15, 799–811

2.   Getting in and out of mitosis with Polo-like kinase-1 Oncogene 2005: 24, 2844–2859

3.   Mitotic Activation of the Kinase Aurora-A Requires Its Binding Partner Bora Developmental Cell 2006: 11, 147–157