新功能活动p21 CDK抑制剂的家庭。
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腊八J,加勒特医学博士,史蒂文森低频,Slingerland JM, Sandhu C,周HS, Fattaey,哈洛E
新功能活动p21 CDK抑制剂的家庭。
基因Dev。1997年4月1;11 (7):847 - 62。
- PubMed ID
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9106657 (在PubMed]
- 文摘
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到协会与细胞周期蛋白形成型功能性激酶复合物是相对低效。这导致了议会的建议可能是一个监管的一步。p21在这份报告我们证明CDK抑制剂(CIP)、p27 (KIP), p57 (KIP2)所有促进协会到型细胞周期蛋白。这种影响具体,不发生与其他cdk抑制剂或cdk-binding蛋白质。体内和体外组装到/细胞周期素D复杂丰富的增加直接与抑制剂水平增加。促进大会并不是由于一个简单的细胞周期阻断和需要cdk和cyclin-binding域的功能。动力学研究表明p21和p27导致35 - 80倍增加K (a),分别的减少主要是因为K(了)。p21在低浓度,促进活动激酶复合物的组装,而在较高的浓度,它能抑制活动。此外,immunodepletion实验表明,大多数活跃的cdk4-associated激酶活性还与p21的同事。来证实这些结果在自然环境中,我们检查在乳腺上皮细胞内源复合物的组装从G(0)释放被捕。 In agreement with our other data, cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes. This complex assembly occurs in parallel to an increase in cyclin D1-associated kinase activity. Immunodepletion experiments demonstrate that most of the cellular cyclin D1-associated kinase activity is also p21 associated. Finally, we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus. We suggest that in addition to their roles as inhibitors, the p21 family of proteins, originally identified as inhibitors, may also have roles as adaptor proteins that assemble and program kinase complexes for specific functions.