Maniswami Radhika Radha, Prashanth Seema, Karanth Archana Venkataramana, Koushik Sindhu, Govindaraj Hemalatha, Mullangi Ramesh, Rajagopal Sriram, Jegatheesan Sooriya Kumar
a Jubilant Biosys Ltd, Bioinformatics , Bangalore , India.
Expert Opin Ther Targets. 2018 Jan;22(1):59-73. doi: 10.1080/14728222.2018.1410140. Epub 2017 Nov 29.
Polo like kinase (PLK) is known to play a pivotal role in various cell cycle processes to perpetuate proper division and growth of the cells. Polo like kinase-4 (PLK4) is one such kinase that appears in low abundance and plays a well-characterized role in centriole duplication. PLK4 deregulation (i.e. both overexpression and depletion of PLK4), leads to altered mitotic fidelity and thereby triggers tumorigenesis. Hence, over the last few years PLK4 has emerged as a potential therapeutic target for the treatment of various advanced cancers. Areas covered: In this review, we discuss the basic structure, expression, localization and functions of PLK4 along with its regulation by various proteins. We also discuss the role of altered PLK4 activity in the onset of cancer and the current pre-clinical and clinical inhibitors to regulate PLK4. Expert opinion: PLK4 mediated centriole duplication has a crucial role in maintaining mitotic correctness in normal cells, while its deregulation has a greater impact on genesis of cancer. Henceforth, a deep knowledge of the PLK4 levels, its role and interactions with various proteins in cancer is required to design effective inhibitors for clinical use.
已知Polo样激酶(PLK)在各种细胞周期进程中发挥关键作用,以维持细胞的正常分裂和生长。Polo样激酶4(PLK4)就是这样一种激酶,其丰度较低,在中心粒复制中发挥着明确的作用。PLK4失调(即PLK4的过表达和缺失)会导致有丝分裂保真度改变,从而引发肿瘤发生。因此,在过去几年中,PLK4已成为治疗各种晚期癌症的潜在治疗靶点。涵盖领域:在本综述中,我们讨论了PLK4的基本结构、表达、定位和功能,以及它受各种蛋白质的调控。我们还讨论了PLK4活性改变在癌症发生中的作用,以及目前用于调节PLK4的临床前和临床抑制剂。专家观点:PLK4介导的中心粒复制在维持正常细胞有丝分裂正确性方面具有关键作用,而其失调对癌症发生有更大影响。因此,需要深入了解PLK4水平、其在癌症中的作用以及与各种蛋白质的相互作用,以设计出有效的临床用抑制剂。