GROWTH SUPPRESSION BY P18, A P16(INK4/MTS1)-RELATED AND P14(INK4B/MTS2)-RELATED CDK6 INHIBITOR, CORRELATES WITH WILD-TYPE PRB FUNCTION
GROWTH SUPPRESSION BY P18, A P16(INK4/MTS1)-RELATED AND P14(INK4B/MTS2)-RELATED CDK6 INHIBITOR, CORRELATES WITH WILD-TYPE PRB FUNCTION
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DOI：
10.1101/gad.8.24.2939
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发表时间：
1994-12-15
影响因子：
10.5
通讯作者：
XIONG, Y
中科院分区：
文献类型：
--
作者：
GUAN, KL;JENKINS, CW;XIONG, Y
D 型细胞周期蛋白依赖性激酶 CDK4 和 CDK6 与许多小细胞蛋白（p14、p15、p16、p18 和 p20）复合。我们分离了与编码 CDK4 和 CDK6 相关 p14 蛋白的 MTS2 基因组片段相对应的 cDNA 序列。通过使用酵母相互作用筛选来寻找 CDK6 相互作用蛋白，我们还鉴定了一种 18 kD 人类蛋白 p18，它是细胞周期蛋白 D-CDK4 抑制剂 p16 (INK4A/MTS1) 和 p14 (MTS2/INK4B) 的同源物。在体内和体外，p18 与 CDK6 相互作用强烈，与 CDK4 相互作用较弱，并且与其他已知 CDK 没有表现出可检测到的相互作用。重组 p18 抑制细胞周期蛋白 D-CDK6 的激酶活性。与与细胞周期蛋白-CDK 形成三元复合物的 CDK 抑制剂 p21/p27 家族不同，仅发现 p14、p16 和 p18 的二元复合物与 CDK4 和/或 CDK6 相关。 p18 或 p16 的异位表达抑制细胞生长，并与内源野生型 pRb 相关。
The D-type cyclin-dependent kinases CDK4 and CDK6 are complexed with many small cellular proteins (p14, p15, p16, p18, and p20). We have isolated cDNA sequences corresponding to the MTS2 genomic fragment that encodes the CDK4- and CDK6-associated p14 protein. By use of a yeast interaction screen to search for CDK6-interacting proteins, we have also identified an 18-kD human protein, p18, that is a homolog of the cyclin D-CDK4 inhibitors p16 (INK4A/MTS1) and p14 (MTS2/INK4B). Both in vivo and in vitro, p18 interacts strongly with CDK6, weakly with CDK4, and exhibits no detectable interaction with the other known CDKs. Recombinant p18 inhibits the kinase activity of cyclin D-CDK6. Distinct from the p21/p27 family of CDK inhibitors that form ternary complexes with cyclin-CDKs, only binary complexes of p14, p16, and p18 were found in association with CDK4 and/or CDK6. Ectopic expression of p18 or p16 suppresses cell growth with a correlated dependence on endogenous wild-type pRb.