Location, location, location: The role of cyclin D1 nuclear localization in cancer
Location, location, location: The role of cyclin D1 nuclear localization in cancer
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DOI：
10.1002/jcb.20613
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发表时间：
2005-12-01
影响因子：
4
通讯作者：
Diehl, JA
中科院分区：
文献类型：
--
作者：
Gladden, AB;Diehl, JA
细胞增殖的控制在维持细胞稳态中是至关重要的，并且该机制的丧失是癌细胞的主要标志。生长因子信号传导的主要靶点是细胞周期蛋白D1依赖性激酶（D1-CDK 4/6），其活性通过使视网膜母细胞瘤蛋白（Rb）沿着相关口袋蛋白107和p130磷酸化来促进G1期进展，从而缓解E2 F家族转录因子的抑制。细胞周期蛋白D1的积累在多个水平上受到调节，包括转录、翻译后激活和整个细胞周期的细胞定位。虽然在许多人类癌症中观察到细胞周期蛋白D1的过表达，但过表达D1的小鼠癌症模型未能建立细胞周期蛋白D1在恶性表型起始中的作用，这表明存在防止细胞周期蛋白D1驱动的癌症的额外调节机制。本文将提出一个概述目前的数据调查调节细胞周期蛋白D1核定位和这些畸变的癌症的患病率。最后，未来的研究途径，涉及细胞周期蛋白D1的细胞定位和其在癌症中的调节将得到解决。
The control of cell proliferation is crucial in maintaining cellular homeostasis and loss of this mechanism is a principle hallmark of cancer cells. A primary target of growth factor signaling is the cyclin D1-dependent kinase (D1-CDK4/6) whose activity promotes G, phase progression by phosphorylating the retinoblastoma protein (Rb) along with related pocket proteins 107 and p130, relieving inhibition of E2F family transcription factors. Cyclin D1 accumulation is regulated at multiple levels including transcription, post-translational activation and cellular localization throughout the cell cycle. While overexpression of cyclin D1 has been observed in a number of human cancers, mouse cancer models overexpressing D1 have fallen short of establishing a role for cyclin D1 in the initiation of malignant phenotypes suggesting an additional regulatory mechanism exists that prevents cyclin D1-driven cancer. This article will present an overview of current data investigating the regulation of cyclin D1 nuclear localization and the prevalence of these aberrations in cancer. Finally, future avenues of research involving cyclin D1 cellular localization and its regulation in cancer will be addressed.