Dutto Ilaria, Tillhon Micol, Cazzalini Ornella, Stivala Lucia A, Prosperi Ennio
Genome Stability Group, Institute of Molecular Genetics, National Research Council (CNR), Via Abbiategrasso 207, 27100, Pavia, Italy.
Arch Toxicol. 2015 Feb;89(2):155-78. doi: 10.1007/s00204-014-1430-4. Epub 2014 Dec 17.
The cell cycle inhibitor p21(CDKN1A) is a protein playing multiple roles not only in the DNA damage response, but also in many cellular processes during unperturbed cell growth. The main, well-known function of p21 is to arrest cell cycle progression by inhibiting the activity of cyclin-dependent kinases. In addition, p21 is involved in the regulation of transcription, apoptosis, DNA repair, as well as cell motility. However, p21 appears to a have a dual-face behavior because, in addition to its tumor suppressor functions, it may act as an oncogene, depending on the cell type and on the cellular localization. As a biomarker of the cell response to different toxic stimuli, p21 expression and functions have been analyzed in an impressive number of studies investigating the activity of several types of chemicals, in order to determine their possible harmful effects on human cells. Here, we review these studies in order to highlight the different roles p21 may play in the cell response to chemical exposure and to better evaluate the information provided by this biomarker.
细胞周期抑制剂p21（CDKN1A）是一种不仅在DNA损伤反应中，而且在细胞正常生长过程中的许多细胞进程中都发挥多种作用的蛋白质。p21的主要且广为人知的功能是通过抑制细胞周期蛋白依赖性激酶的活性来阻止细胞周期进程。此外，p21还参与转录调控、细胞凋亡、DNA修复以及细胞运动。然而，p21似乎具有两面性，因为除了其肿瘤抑制功能外，根据细胞类型和细胞定位，它可能还充当癌基因。作为细胞对不同毒性刺激反应的生物标志物，在大量研究几种化学物质活性的研究中分析了p21的表达和功能，以确定它们对人类细胞可能产生的有害影响。在此，我们回顾这些研究，以突出p21在细胞对化学物质暴露反应中可能发挥的不同作用，并更好地评估该生物标志物提供的信息。
