Department of General and Visceral Surgery, Surgery Center, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Department of Biology, School of Science and Technology, Nazarbayev University, 53 Kabanbay Batyr Ave, Nur-Sultan 020000, Kazakhstan.
Gene. 2019 Oct 5;715:144005. doi: 10.1016/j.gene.2019.144005. Epub 2019 Jul 31.
Members of the highly conserved pleiotropic CK1 family of serine/threonine-specific kinases are tightly regulated in the cell and play crucial regulatory roles in multiple cellular processes from protozoa to human. Since their dysregulation as well as mutations within their coding regions contribute to the development of various different pathologies, including cancer and neurodegenerative diseases, they have become interesting new drug targets within the last decade. However, to develop optimized CK1 isoform-specific therapeutics in personalized therapy concepts, a detailed knowledge of the regulation and functions of the different CK1 isoforms, their various splice variants and orthologs is mandatory. In this review we will focus on the stress-induced CK1 isoform delta (CK1δ), thereby addressing its regulation, physiological functions, the consequences of its deregulation for the development and progression of diseases, and its potential as therapeutic drug target.
高度保守的多效 CK1 丝氨酸/苏氨酸特异性激酶家族的成员在细胞中受到严格调控，在从原生动物到人等多种细胞过程中发挥着关键的调节作用。由于它们的失调以及其编码区域内的突变导致了各种不同的病理学的发展，包括癌症和神经退行性疾病，因此在过去十年中，它们已成为新的有趣的药物靶点。然而，为了在个性化治疗概念中开发优化的 CK1 同工型特异性治疗方法，详细了解不同 CK1 同工型、其各种剪接变体和同源物的调节和功能是必不可少的。在这篇综述中，我们将重点介绍应激诱导的 CK1 同工型 δ（CK1δ），从而探讨其调节、生理功能、其失调对疾病发展和进展的影响，以及作为治疗药物靶点的潜力。
