P21 and p27: roles in carcinogenesis and drug resistance.
P21 and p27: roles in carcinogenesis and drug resistance.
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DOI：
10.1017/s1462399408000744
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发表时间：
2008-07-01
影响因子：
6.2
通讯作者：
Park BH
中科院分区：
文献类型：
--
作者：
Abukhdeir AM;Park BH
人类癌症是由细胞生长和细胞死亡的不平衡引起的。控制这种平衡的关键蛋白质是那些介导细胞周期的蛋白质。已经鉴定了几种不同的分子效应物，其严格调节细胞周期的特定阶段，包括细胞周期蛋白、细胞周期蛋白依赖性激酶（CDK）和CDK抑制剂。值得注意的是，两种G1-检查点CDK抑制剂- p21（CDKN 1A）和p27（CDKN 1B）-的表达或功能丧失与许多人类恶性肿瘤的发生或进展有关。此外，越来越多的证据表明p21或p27的功能丧失可以介导耐药表型。然而，文献中的报告也表明p21和p27可以促进肿瘤，这表明了一种自相矛盾的效应。本文综述了这两种CDK抑制剂的历史和最新研究，包括它们的识别、功能、在肿瘤发生中的重要性以及它们在耐药中的作用。
Human cancers arise from an imbalance of cell growth and cell death. Key proteins that govern this balance are those that mediate the cell cycle. Several different molecular effectors have been identified that tightly regulate specific phases of the cell cycle, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors. Notably, loss of expression or function of two G1-checkpoint CDK inhibitors - p21 (CDKN1A) and p27 (CDKN1B) - has been implicated in the genesis or progression of many human malignancies. Additionally, there is a growing body of evidence suggesting that functional loss of p21 or p27 can mediate a drug-resistance phenotype. However, reports in the literature have also suggested p21 and p27 can promote tumours, indicating a paradoxical effect. Here, we review historic and recent studies of these two CDK inhibitors, including their identification, function, importance to carcinogenesis and finally their roles in drug resistance.