P27, A NOVEL INHIBITOR OF G1 CYCLIN-CDK PROTEIN-KINASE ACTIVITY, IS RELATED TO P21

P27, A NOVEL INHIBITOR OF G1 CYCLIN-CDK PROTEIN-KINASE ACTIVITY, IS RELATED TO P21
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DOI:
10.1016/0092-8674(94)90573-8
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发表时间:
1994-07-15
期刊:
影响因子:
64.5
通讯作者:
HUNTER, T
HUNTER, T
中科院分区:
生物学1区
文献类型:
--
作者:
TOYOSHIMA, H;HUNTER, T

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利用酵母相互作用筛选来寻找与细胞周期蛋白D1-Cdk4相互作用的蛋白,我们发现了一个27 kDa的与p21细胞周期蛋白- cdk抑制剂相关的小鼠蛋白。p27与d型细胞周期蛋白和Cdk4的相互作用较强,与细胞周期蛋白E和Cdk2的相互作用较弱。在小鼠成纤维细胞中,p27主要与细胞周期蛋白D1-Cdk4相关。重组p27是细胞周期蛋白D1-Cdk4和细胞周期蛋白a - cdk2蛋白激酶活性的有效抑制剂,是细胞周期蛋白B1-Cdc2的较弱抑制剂。p27在Saos-2细胞中的过度表达导致G1阻滞。P27蛋白水平不会随着血清刺激的静止小鼠成纤维细胞在细胞周期中的进展而改变。p27与p27(Kip1)相同,p27(Kip1)是一种细胞周期蛋白- cdk抑制剂,存在于TGF β处理的细胞中。p27具有G1进程负调控的特征,并可能介导TGF β诱导的G1停滞。
Using a yeast interaction screen to search for proteins that interact with cyclin D1-Cdk4, we identified a 27 kDa mouse protein related to the p21 cyclin-Cdk inhibitor. p27 interacts strongly with D-type cyclins and Cdk4 in vitro and more weakly with cyclin E and Cdk2. In mouse fibroblasts, p27 is associated predominantly with cyclin D1-Cdk4. Recombinant p27 is a potent inhibitor of cyclin D1-Cdk4 and cyclin A-Cdk2 protein kinase activity and a weaker inhibitor of cyclin B1-Cdc2. Overexpression of p27 in Saos-2 cells causes G1 arrest. p27 protein levels do not change as serum-stimulated quiescent mouse fibroblasts progress through the cell cycle. p27 is identical to p27(Kip1), a cyclin-Cdk inhibitor present in TGF beta-treated cells. p27 has the hallmarks of a negative regulator of G1 progression and may mediate TGF beta-induced G1 arrest.