The role of p27Kip1 in maintaining the levels of D-type cyclins in vivo
The role of p27Kip1 in maintaining the levels of D-type cyclins in vivo
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DOI：
10.1016/j.bbamcr.2004.01.001
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发表时间：
2004-05-03
影响因子：
5.1
通讯作者：
Hampl, A
中科院分区：
文献类型：
--
作者：
Bryja, V;Pacherník, J;Hampl, A
本实验采用p27缺陷小鼠进行体内实验，研究p27对分化细胞中d型细胞周期蛋白代谢的意义。p27缺失导致某些器官中细胞周期蛋白D2和/或D3水平降低。睾丸间质细胞表明，这种依赖性仅局限于某些类型的细胞，包括终末分化的细胞，这些细胞中缺乏p27会干扰它们的分化。在非突变动物中，由于p27缺失导致的细胞周期蛋白D的减少相当于与p27物理相关的细胞周期蛋白D的数量。数据表明p27相关的细胞周期蛋白D的比例决定了对p27缺乏的反应。d型细胞周期蛋白水平依赖于p27的细胞在p27缺失时不会上调其CDK2和CDK4的活性，并且在正常情况下，这些细胞中与CDK2和/或周期蛋白a /E结合的p27量可以忽略不计。总之，这些发现表明p27存在双重作用，一个是通过抑制细胞周期蛋白依赖性激酶（CDK）对细胞周期进行经典调节，另一个是参与与d型细胞周期蛋白一起实现的分化状态的建立和/或维持。(C) 2004 Elsevier B.V.版权所有
This in vivo study employs p27-deficient mice to investigate the significance of p27 for the metabolism of D-type cyclins in differentiated cells. The absence of p27 results in decreased levels of cyclins D2 and/or D3 in some organs. As demonstrated on Leydig cells of testis, such dependency is only restricted to certain cell types including terminally differentiated ones, and the absence of p27 in these cells can interfere with their differentiation. The decrease of cyclin D caused by the absence of p27 equals the amount of cyclin D physically associated with p27 in non-mutant animals. The data indicate that it is the proportion of p27-associated cyclin D that determines the response to p27 deficiency. Cells in which the level of D-type cyclin is dependent on p27 do not up-regulate the activity of their CDK2 and CDK4 upon loss of p27, and these cells have a negligible amount of p27 bound to CDK2 and/or cyclin A/E under normal conditions. Together, the findings suggest the existence of a dual role for p27, one being a classical regulation of cell cycle via inhibition of cyclin-dependent kinases (CDK), and the other being participation in the establishment and/or maintenance of differentiated status that is realized in conjunction with D-type cyclins. (C) 2004 Elsevier B.V. All rights reserved.