CK2 Inhibitors and the DYRK Family Protein Kinases. In “Protein Kinase CK2 Cellular Function in Normal and Disease States”, Eds. K. Ahmed, O.-G. Issinger, and R. Szyska
CK2 Inhibitors and the DYRK Family Protein Kinases. In “Protein Kinase CK2 Cellular Function in Normal and Disease States”, Eds. K. Ahmed, O.-G. Issinger, and R. Szyska
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CK2 抑制剂和 DYRK 家族蛋白激酶。《正常和疾病状态下的蛋白激酶 CK2 细胞功能》，K. Ahmed、O.-G 和 R. Szyska 编着。
DOI：
10.1007/978-3-319-14544-0_19
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Y.
中科院分区：
文献类型：
--
作者：
Miyata;Y.
CK 2是一种普遍存在的多效性丝氨酸/苏氨酸靶向嗜酸性蛋白激酶。CK 2在恶性肿瘤细胞的异常增殖中起重要作用。由于CK 2的组成性活性，其抑制剂已被广泛用于分析CK 2在细胞系统中的生理功能。此外，CK 2抑制剂被认为是有希望的癌症化疗候选物。最近，几种常用的CK 2抑制剂已被证明可以抑制DYRK（双特异性酪氨酸磷酸化调节蛋白激酶）家族蛋白激酶。因此，考虑到常规CK 2抑制剂对DYRKs的影响，应仔细解释其结果。在本章中，在CK 2及其抑制剂的介绍部分之后，描绘了DYRK家族蛋白激酶的结构和激活机制。DYRK 1A是人类21号染色体上唐氏综合征关键区编码的关键因子之一，DYRK 1A的调节异常可能是唐氏综合征患者中观察到的各种表型的分子基础。详细描述了DYRK 1A的底物、生理功能、结合伴侣、调节机制和CK 2抑制剂敏感性。最后，将讨论CK 2和DYRK 1A作为治疗靶点的生物学和临床重要性。
CK2 is a ubiquitous and pleiotropic Ser-/Thr-targeting acidophilic protein kinase. CK2 plays an important role in the aberrant proliferation of malignant cancer cells. Because of constitutive activity of CK2, its inhibitors have been widely used to analyze the physiological function of CK2 in cellular systems. In addition, CK2 inhibitors are regarded as promising cancer chemotherapeutic candidates. Recently, several commonly used CK2 inhibitors have been shown to suppress DYRK (dual-specificity tyrosine-phosphorylation-regulated protein kinase) family protein kinases. Thus, the results obtained with conventional CK2 inhibitors should be carefully interpreted considering their effects on DYRKs. In this chapter, after an introductory section on CK2 and its inhibitors, the structures and activation mechanism of DYRK family protein kinases are portrayed. DYRK1A is one of the pivotal factors encoded in Down’s syndrome critical region on human chromosome 21, and dysregulation of DYRK1A may be a molecular basis of various phenotypes observed in Down’s syndrome patients. Substrates, physiological function, binding partners, regulatory mechanisms, and CK2 inhibitor sensitivities of DYRK1A are described in detail. Finally, the biological and clinical importance of CK2 and DYRK1A as therapeutic targets will be discussed.