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首页> 外文期刊>Molecular and Cellular Biology >Caspase-Dependent Regulation and Subcellular Redistribution of the Transcriptional Modulator YY1 during Apoptosis
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Caspase-Dependent Regulation and Subcellular Redistribution of the Transcriptional Modulator YY1 during Apoptosis

机译：凋亡过程中转录调节因子YY1的半胱天冬酶依赖性调节和亚细胞再分布。

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The transcriptional regulator Yin Yang 1 (YY1) controls many aspects of cell behavior and is essential for development. We analyzed the fate of YY1 during apoptosis and studied the functional consequences. We observed that this factor is rapidly translocated into the cell nucleus in response to various apoptotic stimuli, including activation of Fas, stimulation by tumor necrosis factor, and staurosporine and etoposide treatment. Furthermore, YY1 is cleaved by caspases in vitro and in vivo at two distinct sites, IATD12G and DDSD119G, resulting in the deletion of the first 119 amino acids early in the apoptotic process. This activity generates an N-terminally truncated YY1 fragment (YY1Δ119) that has lost its transactivation domain but retains its DNA binding domain. Indeed, YY1Δ119 is no longer able to stimulate gene transcription but interacts with DNA. YY1Δ119 but not the wild-type protein or the caspase-resistant mutant YY1D12A/D119A enhances Fas-induced apoptosis, suggesting that YY1 is involved in a positive feedback loop during apoptosis. Our findings provide evidence for a new mode of regulation of YY1 and define a novel aspect of the involvement of YY1 in the apoptotic process.
机译：转录调节因子Yin Yang 1（YY1）控制细胞行为的许多方面，并且对于发育至关重要。我们分析了细胞凋亡过程中YY1的命运，并研究了其功能后果。我们观察到，响应各种凋亡刺激，包括激活Fas，肿瘤坏死因子刺激以及星形孢菌素和依托泊苷治疗，该因子迅速转移到细胞核中。此外，YY1在体内和体内的半胱天冬酶在IATD 12 G和DDSD 119 G的两个不同位点被裂解，导致早期的119个氨基酸被删除。在凋亡过程中。该活性产生了N末端截短的YY1片段（YY1Δ119），该片段失去了其反式激活结构域，但保留了其DNA结合结构域。实际上，YY1Δ119不再能够刺激基因转录，而是与DNA相互作用。 YY1Δ119而非野生型蛋白或耐半胱天冬酶的突变体YY1D12A / D119A增强Fas诱导的凋亡，提示YY1参与凋亡过程中的正反馈回路。我们的发现为YY1的新调节模式提供了证据，并定义了YY1参与凋亡过程的一个新方面。

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