Overexpression of CR/periphilin downregulates Cdc7 expression and induces S-phase arrest

Overexpression of CR/periphilin downregulates Cdc7 expression and induces S-phase arrest
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DOI:
10.1016/j.bbrc.2004.09.083
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发表时间:
2004-11-12
影响因子:
3.1
通讯作者:
Matsuoka, M
Matsuoka, M
中科院分区:
生物学4区
文献类型:
--
作者:
Kurita, M;Suzuki, H;Matsuoka, M

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Cdc7表达抑制因子(CR)/periphilin最初被克隆为与凝固细胞包膜前体periplakin的相互作用因子,并被认为构成一种新型的核基质。我们发现CR/periphilin是一种普遍表达的核蛋白,具有斑点状分布。过表达CR/periphilin诱导s期阻滞。对参与DNA复制的调节因子的表达分析表明,DNA复制起始和持续的调节因子Cdc7的mRNA和蛋白表达均因CR/periphilin的过表达而显著下调。然而,Cdc7的共表达只能轻微地挽救CR诱导的s期阻滞,这表明CR通过改变包括Cdc7在内的一些基因的表达来延缓s期进展,这些基因参与DNA复制的进展或DNA复制与s期进展的协调。(C) 2004爱思唯尔公司版权所有。
Cdc7 expression repressor (CR)/periphilin has been originally cloned as an interactor with periplakin, a precursor of the cornified cell envelope, and suggested to constitute a new type of nuclear matrix. We here show that CR/periphilin is a ubiquitously expressed nuclear protein with speckled distribution. Overexpression of CR/periphilin induces S-phase arrest. Analysis of expression of regulators involved in DNA replication has revealed that both mRNA and protein expression of Cdc7, a regulator of the initiation and continuation of DNA replication, are markedly downregulated by overexpression of CR/periphilin. However, co-expression of Cdc7 only marginally rescues S-phase arrest induced by CR, indicating that CR retards S-phase progression by modifying expression of some genes including Cdc7, which are involved in progression of DNA replication or coordination of DNA replication and S-phase progression. (C) 2004 Elsevier Inc. All rights reserved.