Interaction of Heat Shock Protein Cpn10 with the Cyclin E/Cdk2 Substrate Nuclear Protein Ataxia-Telangiectasia (NPAT) Is Involved in Regulating Histone Transcription.
Interaction of Heat Shock Protein Cpn10 with the Cyclin E/Cdk2 Substrate Nuclear Protein Ataxia-Telangiectasia (NPAT) Is Involved in Regulating Histone Transcription.
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热休克蛋白 Cpn10 与细胞周期蛋白 E/Cdk2 底物核蛋白共济失调毛细血管扩张 (NPAT) 的相互作用参与调节组蛋白转录。
DOI：
10.1074/jbc.m115.659201
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发表时间：
2015-12-04
期刊：
影响因子：
--
通讯作者：
Luo Y
中科院分区：
文献类型：
--
作者：
Ling Zheng L;Wang FY;Cong XX;Shen Y;Rao XS;Huang DS;Fan W;Yi P;Wang XB;Zheng L;Zhou YT;Luo Y
背景：NPAT 对于组蛋白转录和细胞周期进展至关重要。结果：一种新型 NPAT 相互作用蛋白 Cpn10/HSPE 对于组蛋白转录和 NPAT 焦点形成至关重要。结论：热休克蛋白Cpn10是组蛋白转录和细胞增殖的新型调节因子。意义：我们的研究结果揭示了热休克蛋白在调节组蛋白转录中的先前未被认识到的作用。组蛋白基因转录的精确调节对于细胞周期进展至关重要。作为 Cyclin E/CDK2 的直接底物，核蛋白共济失调毛细血管扩张 (NPAT) 是调节组蛋白转录和细胞周期进程的关键因素。在这里，我们发现 Cpn10/HSPE（一种 10 kDa 热休克蛋白）是 NPAT 的新型相互作用伙伴。在细胞核的 G1 和 S 期期间，Cpn10 池与 NPAT 焦点共定位。功能获得和功能丧失实验揭示了 Cpn10 在组蛋白转录中的重要作用。 Cpn10 内的保守 DLFD 基序对于靶向 NPAT 和调节组蛋白转录至关重要。更重要的是，Cpn10 的敲低破坏了 NPAT 和 FADD 样白细胞介素 1β 转换酶相关巨蛋白的焦点形成，而不影响 Coilin 阳性 Cajal 小体。最后，Cpn10 对于 S 期进展和细胞增殖很重要。总而言之，我们的发现揭示了 Cpn10 在 NPAT 信号传导空间调控中的新作用，并揭示了热休克蛋白和组蛋白转录调控之间以前未被认识到的联系。
Background: NPAT is critical for histone transcription and cell cycle progression. Results: A novel NPAT-interacting protein, Cpn10/HSPE, is critical for histone transcription and focus formation of NPAT. Conclusion: Heat shock protein Cpn10 is a novel regulator for histone transcription and cell proliferation. Significance: Our findings reveal a previously unappreciated role of heat shock protein in regulating histone transcription. Precise modulation of histone gene transcription is critical for cell cycle progression. As a direct substrate of Cyclin E/CDK2, nuclear protein ataxia-telangiectasia (NPAT) is a crucial factor in regulating histone transcription and cell cycle progression. Here we identified that Cpn10/HSPE, a 10-kDa heat shock protein, is a novel interacting partner of NPAT. A pool of Cpn10 is colocalized with NPAT foci during G1 and S phases in nuclei. Gain- and loss-of-function experiments unraveled an essential role of Cpn10 in histone transcription. A conserved DLFD motif within Cpn10 was critical for targeting NPAT and modulating histone transcription. More importantly, knockdown of Cpn10 disrupted the focus formation of both NPAT and FADD-like interleukin-1β-converting enzyme-associated huge protein without affecting Coilin-positive Cajal bodies. Finally, Cpn10 is important for S phase progression and cell proliferation. Taken together, our finding revealed a novel role of Cpn10 in the spatial regulation of NPAT signaling and disclosed a previously unappreciated link between the heat shock protein and histone transcription regulation.