CR/periphilin is a transcriptional co-repressor involved in cell cycle progression

CR/periphilin is a transcriptional co-repressor involved in cell cycle progression
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DOI:
10.1016/j.bbrc.2007.10.090
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发表时间:
2007-12-28
影响因子:
3.1
通讯作者:
Matsuoka, Masaaki
Matsuoka, Masaaki
中科院分区:
生物学4区
文献类型:
--
作者:
Kurita, Megumi;Suzuki, Hiroaki;Matsuoka, Masaaki

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CR/periphilin(CR)主要通过转录抑制Cdc 7(DNA复制的关键调节因子)的表达和部分未知的机制在S期阻滞细胞周期进程。在这项研究中,我们表明,CR的强制表达抑制Cdc 7启动子活性。酵母GAL 4转录因子的DNA结合结构域与CR的连接使CR能够以组蛋白脱乙酰酶(HDAC)活性依赖性方式抑制GAL 4启动子介导的转录。CR与转录阻遏物复合物中的常见组分mSin 3A以及HDAC 1形成复合物,表明CR可能通过与Sin 3/HDAC共阻遏物复合物的功能性相互作用而表现为共阻遏物。我们还表明,CR,CR-S,这是没有一个由CR基因的外显子4编码的区域,是一个弱的相互作用与HDAC 1的选择性剪接的变体,显示CR活性的抑制作用。(C)2007爱思唯尔公司All rights reserved.
CR/periphilin (CR) retards cell cycle progression mainly at the S-phase in part by transcriptionally repressing expression of Cdc7, the key regulator of DNA replication, and in part by unknown mechanisms. In this study, we show that enforced expression of CR inhibits Cdc7 promoter activity. The attachment of the DNA-binding domain of the yeast GAL4 transcription factor to CR that appears without DNA-binding sequences, enables CR to repress GAL4 promoter-mediated transcription in a histone deacetylase (HDAC) activity-dependent manner. CR forms a complex with mSin3A, a common component in transcriptional repressor complexes, as well as with HDAC1, suggesting that CR may behave as a co-repressor by functional interaction with the Sin3/HDAC co-repressor complex. We also demonstrate that an alternatively spliced variant of CR, CR-S, which is without a region encoded by exon 4 of the CR gene and is a weak interactor with HDAC1, shows a suppressing effect on CR activity. (C) 2007 Elsevier Inc. All rights reserved.