细胞周期蛋白依赖性激酶抑制剂p27（KIP1）和p57（KIP2）在组织生长与发育调控中的合作。
Cooperation between the Cdk inhibitors p27(KIP1) and p57(KIP2) in the control of tissue growth and development.
作者信息
Zhang P, Wong C, DePinho R A, Harper J W, Elledge S J
机构信息
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York 10461 USA.
出版信息
Genes Dev. 1998 Oct 15;12(20):3162-7. doi: 10.1101/gad.12.20.3162.
Abstract
Cell cycle exit is required for terminal differentiation of many cell types. The retinoblastoma protein Rb has been implicated both in cell cycle exit and differentiation in several tissues. Rb is negatively regulated by cyclin-dependent kinases (Cdks). The main effectors that down-regulate Cdk activity to activate Rb are not known in the lens or other tissues. In this study, using multiple mutant mice, we show that the Cdk inhibitors p27(KIP1) and p57(KIP2) function redundantly to control cell cycle exit and differentiation of lens fiber cells and placental trophoblasts. These studies demonstrate that p27(KIP1) and p57(KIP2) are critical terminal effectors of signal transduction pathways that control cell differentiation.
摘要
细胞周期退出是许多细胞类型终末分化所必需的。视网膜母细胞瘤蛋白Rb在几种组织的细胞周期退出和分化过程中都发挥了作用。Rb受到细胞周期蛋白依赖性激酶（Cdks）的负调控。在晶状体或其他组织中，下调Cdk活性以激活Rb的主要效应分子尚不清楚。在本研究中，我们使用多种突变小鼠，证明细胞周期蛋白依赖性激酶抑制剂p27（KIP1）和p57（KIP2）发挥冗余功能，以控制晶状体纤维细胞和胎盘滋养层细胞的细胞周期退出和分化。这些研究表明，p27（KIP1）和p57（KIP2）是控制细胞分化的信号转导途径的关键终末效应分子。
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本文引用的文献
1
The retinoblastoma gene family: cousins with overlapping interests.视网膜母细胞瘤基因家族：兴趣重叠的亲属
Trends Genet. 1998 Jun;14(6):223-9. doi: 10.1016/s0168-9525(98)01470-x.
2
Rb binds c-Jun and activates transcription.Rb与c-Jun结合并激活转录。
EMBO J. 1998 Apr 15;17(8):2342-52. doi: 10.1093/emboj/17.8.2342.
3
Sox1 directly regulates the gamma-crystallin genes and is essential for lens development in mice.Sox1直接调控γ-晶状体蛋白基因，对小鼠晶状体发育至关重要。
Genes Dev. 1998 Mar 15;12(6):776-81. doi: 10.1101/gad.12.6.776.
4
Stable binding to E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumor cell growth.视网膜母细胞瘤蛋白激活转录、促进分化和抑制肿瘤细胞生长并不需要与E2F稳定结合。
Genes Dev. 1998 Jan 1;12(1):95-106. doi: 10.1101/gad.12.1.95.
5
Distinct roles for E2F proteins in cell growth control and apoptosis.E2F蛋白在细胞生长控制和细胞凋亡中的不同作用。
Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7245-50. doi: 10.1073/pnas.94.14.7245.
6
Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome.缺乏p57KIP2的小鼠中细胞分化和增殖的改变表明其在贝克威思-维德曼综合征中起作用。
Nature. 1997 May 8;387(6629):151-8. doi: 10.1038/387151a0.
7
Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice.129个亚系之间的遗传变异及其在小鼠定向诱变中的重要性。
Nat Genet. 1997 May;16(1):19-27. doi: 10.1038/ng0597-19.
8
Ablation of the CDK inhibitor p57Kip2 results in increased apoptosis and delayed differentiation during mouse development.在小鼠发育过程中，细胞周期蛋白依赖性激酶抑制剂p57Kip2的缺失会导致细胞凋亡增加和分化延迟。
Genes Dev. 1997 Apr 15;11(8):973-83. doi: 10.1101/gad.11.8.973.
9
Retinoblastoma protein in growth suppression and death protection.视网膜母细胞瘤蛋白在生长抑制和死亡保护中的作用
Curr Opin Genet Dev. 1997 Feb;7(1):39-45. doi: 10.1016/s0959-437x(97)80107-4.
10
Rb functions to inhibit apoptosis during myocyte differentiation.Rb在心肌细胞分化过程中发挥抑制细胞凋亡的作用。
Cancer Res. 1997 Feb 1;57(3):351-4.
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