Interaction of FLASH with Arsenite Resistance Protein 2 Is Involved in Cell Cycle Progression at S Phase
Interaction of FLASH with Arsenite Resistance Protein 2 Is Involved in Cell Cycle Progression at S Phase
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DOI：
10.1128/mcb.00289-09
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发表时间：
2009-09-01
影响因子：
5.3
通讯作者：
Yonehara, Shin
中科院分区：
文献类型：
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作者：
Kiriyama, Maria;Kobayashi, Yohei;Yonehara, Shin
研究表明，FLASH是S期进展所需的，并与核蛋白、共济失调-毛细血管扩张基因座（NPAT）相互作用，NPAT是细胞核中卡哈尔体的一种成分，也是组蛋白转录的激活剂。我们研究了人类FLASH的作用，通过使用诱导型FLASH敲低系统在存在或不存在各种突变形式的小鼠FLASH。虽然不与NPAT相互作用的FLASH的羧基末端缺失突变体可以支持S期进展，但其氨基末端缺失突变体不能自我缔合，不能支持S期进展、复制依赖性组蛋白转录或Cajal小体的形成。此外，FLASH被证明通过其仅由13个氨基酸组成的中心区域与抗砷蛋白2（ARS 2）相关。ARS 2的表达以及FLASH与ARS 2的相互作用是S期进展所必需的。综合这些结果，FLASH通过与ARS 2相互作用在S期进展中发挥作用。
FLASH has been shown to be required for S phase progression and to interact with a nuclear protein, ataxia-telangiectasia locus (NPAT), a component of Cajal bodies in the nucleus and an activator of histone transcription. We investigated the role of human FLASH by using an inducible FLASH knockdown system in the presence or absence of various mutant forms of mouse FLASH. While carboxyl-terminal deletion mutants of FLASH, which do not interact with NPAT, can support S phase progression, its amino-terminal deletion mutants, which are unable to self associate, cannot support S phase progression, replication-dependent histone transcription, or the formation of Cajal bodies. Furthermore, FLASH was shown to be associated with arsenite resistance protein 2 (ARS2) through its central region, which is composed of only 13 amino acids. The expression of ARS2 and the interaction between FLASH and ARS2 are required for S phase progression. Taking these results together, FLASH functions in S phase progression through interaction with ARS2.