Isolation and characterization of p19(INK4d), a p16-related inhibitor specific to CDK6 and CDK4
Isolation and characterization of p19(INK4d), a p16-related inhibitor specific to CDK6 and CDK4
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DOI：
10.1091/mbc.7.1.57
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发表时间：
1996-01-01
影响因子：
3.3
通讯作者：
Xiong, Y
中科院分区：
文献类型：
--
作者：
Guan, KL;Jenkins, CW;Xiong, Y
细胞周期蛋白依赖性激酶4和6在体内与许多小细胞蛋白复合。我们已经分离的cDNA序列，INK 4d，编码一个19 kDa的蛋白质，与CDK 6在几个造血细胞系。p19与p16/INK 4家族的其他已鉴定的抑制剂具有相同的相似性和共同的祖先。p19与CDK 4和CDK 6相互作用并抑制其活性，与其他已知的CDK没有可检测的相互作用。p19蛋白存在于细胞核和细胞质中。p19基因已定位于染色体19p13.2，其mRNA表达水平在不同组织之间差异很大。与p21和p27与CDK亚基的相互作用依赖于或受细胞周期蛋白亚基刺激相反，p19和p18与CDK 6的相互作用受到细胞周期蛋白的阻碍。二元细胞周期蛋白D1-p18/p19或细胞周期蛋白D1-CDK 6复合物是高度稳定的，并且不能被过量的细胞周期蛋白D1或p19/p18蛋白解离，这表明p16抑制剂和D细胞周期蛋白可能以竞争或潜在相互排斥的方式与CDK 4和6相互作用。
Cyclin-dependent kinases 4 and 6 are complexed with many small cellular proteins in vivo. We have isolated cDNA sequences, INK4d, encoding a 19-kDa protein that is associated with CDK6 in several hematopoietic cell lines. p19 shares equal similarity and a common ancestor with other identified inhibitors of the p16/INK4 family. p19 interacts with and inhibits the activity of both CDK4 and CDK6 and exhibits no detectable interaction with the other known CDKs. p19 protein is present in both cell nuclei and cytoplasm. The p19 gene has been mapped to chromosome 19p13.2, and the level of its mRNA expression varies widely between different tissues. In contrast to p21 and p27 whose interaction with CDK subunits is dependent on or stimulated by the cyclin subunit, the interaction of p19 and p18 with CDK6 is hindered by the cyclin protein. Binary cyclin D1-p18/p19 or cyclin D1-CDK6 complexes are highly stable and cannot be dissociated by excess amounts of cyclin D1 or p19/p18 proteins, suggesting that p16 inhibitors and D cyclins may interact with CDKs 4 and 6 in a competing or potentially mutually exclusive manner.