Qie Shuo, Diehl J Alan
Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, Charleston, SC, 29425, USA.
J Mol Med (Berl). 2016 Dec;94(12):1313-1326. doi: 10.1007/s00109-016-1475-3. Epub 2016 Oct 2.
Mammalian cells encode three D cyclins (D1, D2, and D3) that coordinately function as allosteric regulators of cyclin-dependent kinase 4 (CDK4) and CDK6 to regulate cell cycle transition from G1 to S phase. Cyclin expression, accumulation, and degradation, as well as assembly and activation of CDK4/CDK6 are governed by growth factor stimulation. Cyclin D1 is more frequently dysregulated than cyclin D2 or D3 in human cancers, and as such, it has been more extensively characterized. Overexpression of cyclin D1 results in dysregulated CDK activity, rapid cell growth under conditions of restricted mitogenic signaling, bypass of key cellular checkpoints, and ultimately, neoplastic growth. This review discusses cyclin D1 transcriptional, translational, and post-translational regulations and its biological function with a particular focus on the mechanisms that result in its dysregulation in human cancers.
哺乳动物细胞编码三种D型细胞周期蛋白（D1、D2和D3），它们协同作为细胞周期蛋白依赖性激酶4（CDK4）和CDK6的变构调节因子，以调节细胞周期从G1期到S期的转变。细胞周期蛋白的表达、积累和降解，以及CDK4/CDK6的组装和激活受生长因子刺激的调控。在人类癌症中，细胞周期蛋白D1比细胞周期蛋白D2或D3更频繁地失调，因此，它得到了更广泛的表征。细胞周期蛋白D1的过表达导致CDK活性失调、在有限的促有丝分裂信号条件下细胞快速生长、绕过关键的细胞检查点，并最终导致肿瘤生长。本综述讨论了细胞周期蛋白D1的转录、翻译和翻译后调控及其生物学功能，特别关注导致其在人类癌症中失调的机制。
