The p97-Ufd1-Npl4 ATPase complex ensures robustness of the G2/M checkpoint by facilitating CDC25A degradation
The p97-Ufd1-Npl4 ATPase complex ensures robustness of the G2/M checkpoint by facilitating CDC25A degradation
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DOI：
10.4161/cc.27779
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发表时间：
2014-03-15
期刊：
影响因子：
4.3
通讯作者：
Meyer, Hemmo
中科院分区：
文献类型：
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作者：
Riemer, Anne;Dobrynin, Grzegorz;Meyer, Hemmo
p97-Ufd 1-Np 14 ATP酶复合物与DNA损伤和复制应激反应有关，但其失活如何导致染色体不稳定性的表现尚不清楚。在这里，我们表明p97-Ufd 1-Np 14在G（2）/M检查点中具有额外的直接作用。在DNA损伤后，p97-Ufd 1-Npl 4通过SCF-β TrCP连接酶结合泛素化下游的CDC 25 A，并促进其蛋白酶体降解。Ufd 1-Np 14的耗尽导致G（2）/M检查点失败，这是由于持续的CDC 25活性和DNA损伤传播到有丝分裂中，对染色体分离具有有害影响。因此，p97-Ufd 1-Np 14是G（2）/M检查点信号传导的组成部分，从而抑制染色体不稳定性。
The p97-Ufd1-Npl4 ATPase complex is associated with the response to DNA damage and replication stress, but how its inactivation leads to manifestation of chromosome instability is unclear. Here, we show that p97-Ufd1-Npl4 has an additional direct role in the G(2)/M checkpoint. Upon DNA damage, p97-Ufd1-Npl4 binds CDC25A downstream of ubiquitination by the SCF-beta TrCP ligase and facilitates its proteasomal degradation. Depletion of Ufd1-Npl4 leads to G(2)/M checkpoint failure due to persistent CDC25 activity and propagation of DNA damage into mitosis with deleterious effects on chromosome segregation. Thus, p97-Ufd1-Npl4 is an integral part of G(2)/M checkpoint signaling and thereby suppresses chromosome instability.