Jiao Yang, Feng Yunpeng, Wang Xiuli
School of Physical Education, Northeast Normal University, Changchun, Jilin, 130024, P. R. China.
Key Laboratory of Molecular Epigenetics, Ministry of Education, Northeast Normal University, Changchun, Jilin, 130024, P. R. China.
Biochemistry (Mosc). 2018 Nov;83(11):1289-1298. doi: 10.1134/S0006297918110019.
CDKN2A is one of the most studied tumor suppressor genes. It encodes the p16-INK4a protein that plays a critical role in the cell cycle progression, differentiation, senescence, and apoptosis. Mutations in CDKN2A or dysregulation of its functional activity are frequently associated with various types of human cancer. As a cyclin-dependent kinase inhibitor, p16-INK4a forms a complex with cyclin-dependent kinases 4/6 (CDK4/6) thereby competing with cyclin D. It is believed that the helix-turn-helix structures in the content of tandem ankyrin repeats in p16-INK4a are required for the protein interaction with CDK4. Until recently, the mechanisms considered to be involved in the regulation of p16-INK4a functions and cancer development have been mutations in DNA, homozygous or heterozygous gene loss, and methylation of CDKN2A promoter region. In this review, we discuss recent findings on the regulation of p16-INK4a by covalent modifications at both transcriptional and post-translational levels.
CDKN2A是研究最多的肿瘤抑制基因之一。它编码p16-INK4a蛋白，该蛋白在细胞周期进程、分化、衰老和凋亡中起关键作用。CDKN2A的突变或其功能活性的失调常与多种人类癌症相关。作为一种细胞周期蛋白依赖性激酶抑制剂，p16-INK4a与细胞周期蛋白依赖性激酶4/6（CDK4/6）形成复合物，从而与细胞周期蛋白D竞争。据信，p16-INK4a中串联锚蛋白重复序列所含的螺旋-转角-螺旋结构是该蛋白与CDK4相互作用所必需的。直到最近，被认为参与p16-INK4a功能调控和癌症发展的机制一直是DNA突变、纯合或杂合基因缺失以及CDKN2A启动子区域的甲基化。在这篇综述中，我们讨论了在转录和翻译后水平上通过共价修饰对p16-INK4a进行调控的最新研究发现。
