LIM Protein Ajuba Participates in the Repression of the ATR-Mediated DNA Damage Response.
LIM Protein Ajuba Participates in the Repression of the ATR-Mediated DNA Damage Response.
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DOI：
10.3389/fgene.2013.00095
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发表时间：
2013
影响因子：
3.7
通讯作者：
Loayza D
中科院分区：
文献类型：
--
作者：
Kalan S;Matveyenko A;Loayza D
LIM蛋白构成了一个以存在LIM结构域为特征的超家族，已知其参与蛋白-蛋白相互作用。我们之前的工作已经暗示了LIM蛋白的Zyxin家族成员，即TRIP6和LPP，在端粒DNA损伤反应（DDR）的抑制中。在这里，我们描述了一个密切相关的LIM分子Ajuba在抑制atr介导的DDR中的作用。我们发现，Ajuba的缺失导致细胞周期的明显延迟，伴随着Rb磷酸化、Chk1磷酸化的增加，p53的诱导和细胞死亡。Ajuba可以在与复制蛋白a （RPA）的复合体中发现，它的缺失导致RPA磷酸化，这是已知的ATR激活的早期事件。我们提出Ajuba通过防止不适当的RPA磷酸化来保护非预定的ATR信号。
LIM proteins constitute a superfamily characterized by the presence of a LIM domain, known to be involved in protein–protein interactions. Our previous work has implicated members of the Zyxin family of LIM proteins, namely TRIP6 and LPP, in the repression of the DNA damage response (DDR) at telomeres. Here, we describe a role for Ajuba, a closely related LIM molecule, in repressing the ATR-mediated DDR. We found that depletion of Ajuba led to apparent delays in the cell cycle, accompanied with increased Rb phosphorylation, Chk1 phosphorylation, induction of p53, and cell death. Ajuba could be found in a complex with replication protein A (RPA), and its depletion led to RPA phosphorylation, known to be an early event in ATR activation. We propose that Ajuba protects against unscheduled ATR signaling by preventing inappropriate RPA phosphorylation.