Roth Aileen, Gihring Adrian, Bischof Joachim, Pan Leiling, Oswald Franz, Knippschild Uwe
University Medical Center Ulm, Department of General, and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
University Medical Center Ulm, Center for Internal Medicine, Department of Internal Medicine I, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Cancers (Basel). 2022 Mar 5;14(5):1345. doi: 10.3390/cancers14051345.
Protein kinases of the Casein Kinase 1 family play a vital role in the regulation of numerous cellular processes. Apart from functions associated with regulation of proliferation, differentiation, or apoptosis, localization of several Casein Kinase 1 isoforms to the centrosome and microtubule asters also implicates regulatory functions in microtubule dynamic processes. Being localized to the spindle apparatus during mitosis Casein Kinase 1 directly modulates microtubule dynamics by phosphorylation of tubulin isoforms. Additionally, site-specific phosphorylation of microtubule-associated proteins can be related to the maintenance of genomic stability but also microtubule stabilization/destabilization, e.g., by hyper-phosphorylation of microtubule-associated protein 1A and RITA1. Consequently, approaches interfering with Casein Kinase 1-mediated microtubule-specific functions might be exploited as therapeutic strategies for the treatment of cancer. Currently pursued strategies include the development of Casein Kinase 1 isoform-specific small molecule inhibitors and therapeutically useful peptides specifically inhibiting kinase-substrate interactions.
酪蛋白激酶1家族的蛋白激酶在众多细胞过程的调控中发挥着至关重要的作用。除了与增殖、分化或凋亡调控相关的功能外，几种酪蛋白激酶1亚型定位于中心体和微管星状体也暗示其在微管动态过程中的调控功能。在有丝分裂期间定位于纺锤体装置的酪蛋白激酶1通过对微管蛋白亚型的磷酸化直接调节微管动态。此外，微管相关蛋白的位点特异性磷酸化可能与基因组稳定性的维持有关，也与微管的稳定/不稳定有关，例如通过微管相关蛋白1A和RITA1的过度磷酸化。因此，干扰酪蛋白激酶1介导的微管特异性功能的方法可能被用作治疗癌症的策略。目前采用的策略包括开发酪蛋白激酶1亚型特异性小分子抑制剂以及特异性抑制激酶-底物相互作用的治疗性有用肽。
