Institute of Pharmacology and Toxicology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
Cell Cycle. 2012 Sep 15;11(18):3389-94. doi: 10.4161/cc.21404. Epub 2012 Aug 23.
Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) constitute an evolutionarily conserved family of protein kinases with key roles in the control of cell proliferation and differentiation. Members of the DYRK family phosphorylate many substrates, including critical regulators of the cell cycle. A recent report revealed that human DYRK2 acts as a negative regulator of G1/S transition by phosphorylating c-Jun and c-Myc, thereby inducing ubiquitination-mediated degradation. Other DYRKs also function as cell cycle regulators by modulating the turnover of their target proteins. DYRK1B can induce reversible cell arrest in a quiescent G0 state by targeting cyclin D1 for proteasomal degradation and stabilizing p27 (Kip1). The DYRK2 ortholog of C. elegans, MBK-2, triggers the proteasomal destruction of oocyte proteins after meiosis to allow the mitotic divisions in embryo development. This review summarizes the accumulating results that provide evidence for a general role of DYRKs in the regulation of protein stability.
双特异性酪氨酸磷酸化调节激酶（DYRKs）是一个进化上保守的蛋白激酶家族，在细胞增殖和分化的调控中起着关键作用。DYRK 家族的成员磷酸化许多底物，包括细胞周期的关键调节因子。最近的一份报告显示，人类 DYRK2 通过磷酸化 c-Jun 和 c-Myc 作为 G1/S 转换的负调节剂，从而诱导泛素介导的降解。其他 DYRKs 也通过调节其靶蛋白的周转率来充当细胞周期调节剂。DYRK1B 可以通过靶向细胞周期蛋白 D1 进行蛋白酶体降解并稳定 p27（Kip1），将细胞不可逆地阻滞在静止的 G0 状态。秀丽隐杆线虫的 DYRK2 同源物 MBK-2 在减数分裂后触发卵母细胞蛋白的蛋白酶体破坏，以允许胚胎发育中的有丝分裂分裂。这篇综述总结了越来越多的结果，这些结果为 DYRKs 在调节蛋白质稳定性方面的普遍作用提供了证据。
