细胞周期蛋白D1、癌症进展与癌症治疗机遇
Cyclin D1, cancer progression, and opportunities in cancer treatment.
作者信息
Qie Shuo, Diehl J Alan
机构信息
Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, Charleston, SC, 29425, USA.
出版信息
J Mol Med (Berl). 2016 Dec;94(12):1313-1326. doi: 10.1007/s00109-016-1475-3. Epub 2016 Oct 2.
Abstract
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.
摘要
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。
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本文引用的文献
1
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Cancer Metab. 2016 Mar 8;4:5. doi: 10.1186/s40170-016-0145-9. eCollection 2016.
2
Metabolic Reprogramming of Pancreatic Cancer Mediated by CDK4/6 Inhibition Elicits Unique Vulnerabilities.CDK4/6抑制介导的胰腺癌代谢重编程引发独特的脆弱性。
Cell Rep. 2016 Feb 9;14(5):979-990. doi: 10.1016/j.celrep.2015.12.094. Epub 2016 Jan 21.
3
The front and rear of collective cell migration.群体细胞迁移的前后。
Nat Rev Mol Cell Biol. 2016 Feb;17(2):97-109. doi: 10.1038/nrm.2015.14. Epub 2016 Jan 4.
4
Targeting CDK4 and CDK6: From Discovery to Therapy.靶向细胞周期蛋白依赖性激酶4和6：从发现到治疗
Cancer Discov. 2016 Apr;6(4):353-67. doi: 10.1158/2159-8290.CD-15-0894. Epub 2015 Dec 11.
5
Complex Coordination of Cell Plasticity by a PGC-1α-controlled Transcriptional Network in Skeletal Muscle.骨骼肌中由PGC-1α控制的转录网络对细胞可塑性的复杂协调
Front Physiol. 2015 Nov 9;6:325. doi: 10.3389/fphys.2015.00325. eCollection 2015.
6
PRMT5-dependent p53 escape in tumorigenesis.肿瘤发生过程中依赖蛋白精氨酸甲基转移酶5（PRMT5）的p53逃逸
Oncoscience. 2015 Aug 31;2(8):700-2. doi: 10.18632/oncoscience.222. eCollection 2015.
7
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Biochim Biophys Acta. 2015 Oct;1849(10):1260-76. doi: 10.1016/j.bbagrm.2015.08.001. Epub 2015 Aug 5.
8
CDK4/6 inhibitors in breast cancer.乳腺癌中的CDK4/6抑制剂
Anticancer Drugs. 2015 Sep;26(8):797-806. doi: 10.1097/CAD.0000000000000249.
9
Tumor progression and the different faces of the PERK kinase.肿瘤进展与PERK激酶的不同面貌
Oncogene. 2016 Mar 10;35(10):1207-15. doi: 10.1038/onc.2015.178. Epub 2015 Jun 1.
10
Targeting cell cycle regulators in hematologic malignancies.靶向血液系统恶性肿瘤中的细胞周期调节剂。
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