Nucleophosmin redistribution following heat shock: a role in heat-induced radiosensitization.
Nucleophosmin redistribution following heat shock: a role in heat-induced radiosensitization.
复制标题
热休克后核磷蛋白的重新分布：在热诱导放射增敏中的作用。
DOI：
10.1158/0008-5472.can-08-4896
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发表时间：
2009
期刊：
影响因子：
11.2
通讯作者：
RotiRoti,JosephL
中科院分区：
文献类型：
--
作者：
Vanderwaal,RobertP;MaggiJr,LeonardB;Weber,JasonD;Hunt,ClaytonR;RotiRoti,JosephL
细胞要从辐射引起的 DNA 损伤中存活下来，需要进入损伤部位来组装修复复合物并进行后续修复，特别是 DNA 双链断裂 (DSB) 的修复。高温会导致细胞核中蛋白质-蛋白质/DNA 相互作用发生变化，从而阻止进入 DNA 损伤部位。本文介绍的研究表明，核仁蛋白核磷蛋白 (NPM) 在热疗后从核仁重新分布，增加其与 DNA 的结合，并阻止接触 DNA DSB。 NPM 的降低显着降低了热诱导的放射增敏作用，但 NPM 水平降低本身并不会改变放射敏感性。 NPM 敲低可减少热诱导的 DNA DSB 修复抑制。此外，这些结果表明 NPM 与热休克细胞中的核基质附着区 DNA 相关。 [癌症研究 2009;69(16):6454–62]
Cellular survival from radiation-induced DNA damage requires access to sites of damage for the assembly of repair complexes and the subsequent repair, particularly the repair of DNA double strand breaks (DSB). Hyperthermia causes changes in protein-protein/DNA interactions in the nucleus that block access to sites of DNA damage. Studies presented here indicate that the nucleolar protein, nucleophosmin (NPM), redistributes from the nucleolus following hyperthermia, increases its association with DNA, and blocks access to DNA DSBs. Reduction of NPM significantly reduces heat-induced radiosensitization, but reduced NPM level does not alter radiation sensitivity per se. NPM knockdown reduces heat-induced inhibition of DNA DSB repair. Also, these results suggest that NPM associates with nuclear matrix attachment region DNA in heat-shocked cells. [Cancer Res 2009;69(16):6454–62]