p27 is regulated independently of Skp2 in the absence of Cdk2.
p27 is regulated independently of Skp2 in the absence of Cdk2.
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DOI：
10.1016/j.bbamcr.2013.11.005
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发表时间：
2014-02
影响因子：
5.1
通讯作者：
Kaldis, Philipp
中科院分区：
文献类型：
--
作者：
Kotoshiba, Shuhei;Gopinathan, Lakshmi;Pfeiffenberger, Elisabeth;Rahim, Anisa;Vardy, Leah A.;Nakayama, Keiko;Nakayama, Keiichi I.;Kaldis, Philipp
周期蛋白依赖性激酶2 （Cdk2）在有丝分裂细胞周期进程中是必不可少的，Cdk2敲除小鼠由于其他Cdks的代偿功能而存活。为了评估Cdk2在限制条件下的作用，我们使用Skp2敲除小鼠，这些小鼠表现出Cdk抑制剂p27Kip1水平升高，p27Kip1能够抑制Cdk2和Cdk1。敲除Cdk2可抑制Skp2−/−小鼠胚胎成纤维细胞的增殖，从而促进我们产生Cdk2−/−Skp2−/−双敲除小鼠。Cdk2−/−Skp2−/−双敲除小鼠是可存活的，并且表现出与Cdk2−/−和Skp2−/−小鼠相似的表型。出乎意料的是，Cdk2−/−Skp2−/−双敲除小鼠产生的成纤维细胞以正常速率增殖。在Skp2−/−mef中观察到的p27的稳定性增加在Cdk2−/−Skp2−/−双敲除成纤维细胞中没有观察到，这表明在缺乏Cdk2的情况下，p27受Skp2独立机制的调节。消融其他泛素连接酶如KPC1、DDB1和Pirh2并不能恢复Cdk2−/−Skp2−/−mef中p27的稳定性。我们的发现指向了p27调控的新途径和替代途径。
Cyclin-dependent kinase 2 (Cdk2) is dispensable for mitotic cell cycle progression and Cdk2 knockout mice are viable due to the compensatory functions of other Cdks. In order to assess the role of Cdk2 under limiting conditions, we used Skp2 knockout mice that exhibit increased levels of Cdk inhibitor, p27Kip1, which is able to inhibit Cdk2 and Cdk1. Knockdown of Cdk2 abrogated proliferation of Skp2−/− mouse embryonic fibroblasts, encouraging us to generate Cdk2−/−Skp2−/− double knockout mice. Cdk2−/−Skp2−/− double knockout mice are viable and display similar phenotypes as Cdk2−/− and Skp2−/− mice. Unexpectedly, fibroblasts generated from Cdk2−/−Skp2−/− double knockout mice proliferated at normal rates. The increased stability of p27 observed in Skp2−/− MEFs was not observed in Cdk2−/−Skp2−/− double knockout fibroblasts indicating that in the absence of Cdk2, p27 is regulated by Skp2-independent mechanisms. Ablation of other ubiquitin ligases for p27 such as KPC1, DDB1, and Pirh2 did not restore stability of p27 in Cdk2−/−Skp2−/− MEFs. Our findings point towards novel and alternate pathways for p27 regulation.
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影响因子：
10.5
作者：
Montagnoli, A;Fiore, F;Pagano, M
通讯作者：
Pagano, M
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
10.5
作者：
POLYAK, K;KATO, JY;KOFF, A
通讯作者：
KOFF, A
影响因子：
64.5
作者：
KATO, JY;MATSUOKA, M;SHERR, CJ
通讯作者：
SHERR, CJ
影响因子：
21.3
作者：
Carrano, AC;Eytan, E;Pagano, M
通讯作者：
Pagano, M