Liu Wan, Li Jun, Song Yu-Shu, Li Yue, Jia Yu-Hong, Zhao Hai-Dong
Department of Breast Surgery, The Second Affiliated Hospital of Dalian Medical University, Zhongshan Road 467, Dalian, 116023, China.
Department of Pathophysiology, Dalian Medical University, Lvshun South Road West 9, Dalian, 116044, China.
Mol Cancer. 2017 Mar 14;16(1):60. doi: 10.1186/s12943-017-0611-1.
As an atypical member of cyclin dependent kinase family, Cyclin dependent kinase 5 (Cdk5) is considered as a neuron-specific kinase in the past decade due to the abundant existence of its activator p35 in post-mitotic neurons. Recent studies show that Cdk5 participates in a series of biological and pathological processes in non-neuronal cells, and is generally dysregulated in various cancer cells. The inhibition or knockdown of Cdk5 has been proven to play an anti-cancer role through various mechanisms, and can synergize the killing effect of chemotherapeutics. DNA damage response (DDR) is a series of regulatory events including DNA damage, cell-cycle arrest, regulation of DNA replication, and repair or bypass of DNA damage to ensure the maintenance of genomic stability and cell viability. Here we describe the regulatory mechanisms of Cdk5, its controversial roles in apoptosis and focus on its links to DDR and cancer.
作为细胞周期蛋白依赖性激酶家族的一个非典型成员，在过去十年中，细胞周期蛋白依赖性激酶5（Cdk5）因其激活剂p35在有丝分裂后神经元中大量存在而被视为一种神经元特异性激酶。最近的研究表明，Cdk5参与非神经元细胞中的一系列生物学和病理过程，并且在各种癌细胞中普遍失调。已证明抑制或敲低Cdk5可通过多种机制发挥抗癌作用，并可增强化疗药物的杀伤效果。DNA损伤反应（DDR）是一系列调节事件，包括DNA损伤、细胞周期停滞、DNA复制调节以及DNA损伤的修复或旁路，以确保基因组稳定性和细胞活力的维持。在这里，我们描述了Cdk5的调节机制、其在细胞凋亡中存在争议的作用，并重点关注其与DDR和癌症的联系。
