Molecular Cancer Genetics & Translational Research Laboratory, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
Molecular Cancer Genetics & Translational Research Laboratory, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
Adv Protein Chem Struct Biol. 2023;134:115-145. doi: 10.1016/bs.apcsb.2022.10.005. Epub 2023 Jan 31.
Aurora-A kinase (AURKA) belongs to the serine/threonine kinase family specific to cell division. In normal cells, activation of the AURKA protein is essential for regulating chromosomal segregation and centrosome maturation. The physiological concentration of AURKA accumulation has utmost importance during cell division. AURKA starts accumulating during the S phase of the cell cycle, gets functionally activated during the G2/M phase, attaches to the microtubule, and gets degraded during mitotic exit. Overexpression of AURKA could lead to deregulated cell cycle division, which is intrinsic to numerous cancers. Moreover, dysregulated AURKA affects various downstream molecules that aid in cancer pathogenesis. AURKA phosphorylates its substrates, including oncoproteins, transcriptional factors, tumor suppressor proteins, or other kinases central to various oncogenic signaling pathways critical to cancer. Considering the central role of AURKA in cell proliferation and tumorigenesis, targeting AURKA can be a novel alternative to cancer management. Several AURKA inhibitors have shown promising responses against different cancers either as a single agent or combined with various therapies. This chapter briefly discusses the role of AURKA and its downstream molecules in cancer vis-à-vis the role of AURKA inhibitor in chemoprevention.
极光激酶 A(AURKA)属于丝氨酸/苏氨酸激酶家族,特异性针对细胞分裂。在正常细胞中,AURKA 蛋白的激活对于调节染色体分离和中心体成熟至关重要。AURKA 的生理浓度在细胞分裂过程中极为重要。AURKA 在细胞周期的 S 期开始积累,在 G2/M 期被功能性激活,附着在微管上,并在有丝分裂结束时降解。AURKA 的过度表达可能导致细胞周期分裂失调,这是许多癌症的内在特征。此外,失调的 AURKA 会影响各种下游分子,这些分子有助于癌症发病机制。AURKA 对其底物进行磷酸化,包括癌蛋白、转录因子、肿瘤抑制蛋白或其他在各种致癌信号通路中起核心作用的激酶,这些通路对癌症至关重要。鉴于 AURKA 在细胞增殖和肿瘤发生中的核心作用,靶向 AURKA 可能成为癌症管理的一种新选择。几种 AURKA 抑制剂已显示出对不同癌症的有希望的反应,无论是作为单一药物还是与各种疗法联合使用。本章简要讨论了 AURKA 及其下游分子在癌症中的作用,以及 AURKA 抑制剂在化学预防中的作用。