Abstract

Polo-like kinase 1 (PLK1) is a conserved mitotic serine-threonine protein kinase, functions as a regulatory protein, and is involved in the progression of the mitotic cycle. It plays important roles in the regulation of cell division, maintenance of genome stability, in spindle assembly, mitosis, and DNA-damage response. PLK1 is consist of a N-terminal serine-threonine kinase domain, and a C-terminal Polo-box domain (regulatory site). The expression of PLK1 is controlled by transcription repressor in the G1 stage and transcription activators in the G2 stage of the cell cycle. Overexpression of PLK1 results in undermining of checkpoints causes excessive cellular division resulting in abnormal cell growth, leading to the development of cancer. Blocking the expression of PLK1 by an antibody, RNA interference, or kinase inhibitors, causes a subsequent reduction in the proliferation of tumour cells and induction of apoptosis in tumour cells without affecting the healthy cells, suggesting an attractive target for drug development. In this review, we discuss detailed information on expression, gene and protein structures, role in different diseases, and progress in the design and development of PLK1 inhibitors. We have performed an in-depth analysis of the PLK1 inhibitors and their therapeutic implications with special focus to the cancer therapeutics.

摘要

Polo 样激酶 1 (PLK1) 是一种保守的有丝分裂丝氨酸-苏氨酸蛋白激酶，作为调节蛋白起作用，并参与有丝分裂周期的进程。它在调节细胞分裂、维持基因组稳定性、纺锤体组装、有丝分裂和 DNA 损伤反应中发挥重要作用。PLK1 由 N 端丝氨酸-苏氨酸激酶域和 C 端 Polo-box 域（调节位点）组成。PLK1 的表达受细胞周期 G1 阶段的转录抑制因子和 G2 阶段的转录激活因子控制。PLK1 的过度表达导致检查点的破坏，导致细胞过度分裂，导致细胞异常生长，导致癌症的发展。通过抗体、RNA 干扰或激酶抑制剂阻断 PLK1 的表达，导致随后肿瘤细胞增殖的减少和肿瘤细胞凋亡的诱导，而不影响健康细胞，这表明它是药物开发的一个有吸引力的目标。在这篇综述中，我们讨论了有关表达、基因和蛋白质结构、在不同疾病中的作用以及 PLK1 抑制剂设计和开发进展的详细信息。我们对 PLK1 抑制剂及其治疗意义进行了深入分析，特别关注癌症治疗。PLK1 抑制剂的设计和开发进展。我们对 PLK1 抑制剂及其治疗意义进行了深入分析，特别关注癌症治疗。PLK1 抑制剂的设计和开发进展。我们对 PLK1 抑制剂及其治疗意义进行了深入分析，特别关注癌症治疗。