D cyclins include three isoforms: D1, D2, and D3. D cyclins heterodimerize with cyclin-dependent kinase 4/6 (CDK4/6) to form kinase complexes that can phosphorylate and inactivate Rb. Inactivation of Rb triggers the activation of E2F transcription factors, which in turn regulate the expression of genes whose products drive cell cycle progression. Because D-type cyclins function as mitogenic sensors that link growth factor signaling directly with G₁ phase progression, it is not surprising that D cyclin accumulation is dysregulated in a variety of human tumors. Elevated expression of D cyclins results from gene amplification, increased gene transcription and protein translation, decreased microRNA levels, and inefficiency or loss of ubiquitylation-mediated protein degradation. This review focuses on the clinicopathological importance of D cyclins, how dysregulation of Ubiquitin-Proteasome System (UPS) contributes to the overexpression of D cyclins, and the therapeutic potential through targeting D cyclin-related machinery in human tumors.

D 细胞周期蛋白包括三种同工型：D1、D2 和 D3。D 细胞周期蛋白与细胞周期蛋白依赖性激酶 4/6 (CDK4/6) 异二聚化形成激酶复合物，可以磷酸化和灭活 Rb。Rb 的失活触发 E2F 转录因子的激活，进而调节其产物驱动细胞周期进程的基因的表达。因为 D 型细胞周期蛋白作为有丝分裂传感器，将生长因子信号与 G ₁直接联系起来相进展，D 细胞周期蛋白积累在各种人类肿瘤中失调也就不足为奇了。D 细胞周期蛋白的表达升高是由基因扩增、基因转录和蛋白质翻译增加、microRNA 水平降低以及泛素化介导的蛋白质降解效率低下或丢失造成的。本综述重点关注 D 细胞周期蛋白的临床病理学重要性、泛素-蛋白酶体系统 (UPS) 的失调如何导致 D 细胞周期蛋白的过度表达，以及通过靶向人类肿瘤中 D 细胞周期蛋白相关机制的治疗潜力。