文章：

癌症中的p21：复杂的网络和多种活动

p21 in cancer: intricate networks and multiple activities

原文发布日期：2009-05-14

DOI: 10.1038/nrc2657

类型: Review Article

开放获取: 否

要点：

1. p21 came into the spotlight as a mediator of p53 tumour suppressor activity and as an inhibitor of cell cycle progression owing to its ability to inhibit the activity of cyclin-dependent kinase (CDK)–cyclin complexes and proliferating cell nuclear antigen (PCNA).
2. The tumour suppressor activity of p21 stems from its role in inducing growth arrest, differentiation or senescence. Recently, it has become apparent that p21 is stimulated by many pathways that are independent of p53.
3. p21 directly regulates gene expression and other cellular events through protein–protein interactions that are independent of CDKs and PCNA.
4. Multiple transcription factors, ubiquitin ligases, and protein kinases regulate the transcription, stability and cellular localization of p21 thereby regulating its activity.
5. Recent data suggest a tumorigenic role of p21 in certain contexts that relies on its ability to suppress apoptosis and promote the assembly of type-D cyclins with CDK4 and CDK6.
6. Given that p21 is a tumour suppressor, but that it behaves as an oncogene in certain cellular contexts, targeting p21 or factors regulating its activity for therapeutic intervention is a promising but challenging task.

要点翻译：

1. p21作为p53肿瘤抑制活性的介导因子以及细胞周期进程的抑制剂而备受关注，这是因为它能够抑制细胞周期蛋白依赖性激酶（CDK）-细胞周期蛋白复合物和增殖细胞核抗原（PCNA）的活性。
2. p21的肿瘤抑制活性源于其在诱导生长停滞、分化或衰老中的作用。最近研究发现，p21受到许多独立于p53的信号通路刺激而被激活。
3. p21通过独立于CDK和PCNA的蛋白质-蛋白质相互作用，直接调控基因表达和其他细胞事件。
4. 多种转录因子、泛素连接酶和蛋白激酶通过调节p21的转录、稳定性和细胞定位来调控其活性。
5. 最新数据显示，p21在特定情境下具有促肿瘤作用，这依赖于其抑制凋亡以及促进D型细胞周期蛋白与CDK4和CDK6组装的能力。
6. 鉴于p21既是肿瘤抑制因子，又在特定细胞环境中表现出癌基因特性，将p21或其活性调控因子作为治疗干预靶点，是一项前景广阔但极具挑战性的任务。

英文摘要：

One of the main engines that drives cellular transformation is the loss of proper control of the mammalian cell cycle. The cyclin-dependent kinase inhibitor p21 (also known as p21WAF1/Cip1) promotes cell cycle arrest in response to many stimuli. It is well positioned to function as both a sensor and an effector of multiple anti-proliferative signals. This Review focuses on recent advances in our understanding of the regulation of p21 and its biological functions with emphasis on its p53-independent tumour suppressor activities and paradoxical tumour-promoting activities, and their implications in cancer.

摘要翻译： 

驱动细胞转化的主要机制之一是对哺乳动物细胞周期正常调控的丧失。细胞周期蛋白依赖性激酶抑制剂p21（也称为p21WAF1/Cip1）可响应多种刺激而促进细胞周期停滞。它在功能上处于有利位置，能够充当多重抗增殖信号的“感受器”和“效应器”。本综述聚焦于p21调控及其生物学功能的最新研究进展，重点阐述其不依赖p53的抑瘤活性以及矛盾的促瘤活性，并探讨其在癌症中的意义。

原文链接：

p21 in cancer: intricate networks and multiple activities