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首页> 外文期刊>Molecular and Cellular Biology >Regulation of Telomerase Activity by Interferon Regulatory Factors 4 and 8 in Immune Cells
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Regulation of Telomerase Activity by Interferon Regulatory Factors 4 and 8 in Immune Cells

机译：免疫细胞中干扰素调节因子4和8对端粒酶活性的调节

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Telomerase activity is downregulated in somatic cells but is upregulated during the activation of cells of the immune system. The mechanism of this reactivation is not well understood. In this study, we demonstrated that interferon regulatory factor 4 (IRF-4) and, to a lesser extent, IRF-8 induce telomerase activity. The suppression of IRF-4 results in decreased levels of TERT (telomerase reverse transcriptase) mRNA and telomerase activity and reduces cell proliferation. The overexpression of TERT compensates for this proliferation defect, suggesting that telomerase contributes to the regulation of cell proliferation by IRF-4. The induction of telomerase by IRF-4 and IRF-8 correlates with the activation of the TERT promoter. IRF-4 binds the interferon response-stimulated element and the gamma interferon-activated sequence composite binding site in the TERT core promoter region in vivo. Additionally, the binding of Sp1, Sp3, USF-1, USF-2, and c-Myc to the TERT promoter is elevated in cells expressing IRF-4. IRF-4, but not IRF-8, synergistically cooperates with Sp1 and Sp3 in the activation of the TERT promoter. Collectively, these results indicate that IRF-4 and IRF-8, two lymphoid cell-specific transcription factors, increase telomerase activity by activating TERT transcription in immune cells.
机译：端粒酶活性在体细胞中被下调，但是在免疫系统细胞的激活过程中被上调。重新激活的机制尚不十分清楚。在这项研究中，我们证明了干扰素调节因子4（IRF-4）和较小程度的IRF-8诱导端粒酶活性。 IRF-4的抑制导致TERT（端粒酶逆转录酶）mRNA和端粒酶活性降低，并降低细胞增殖。 TERT的过表达弥补了这种增殖缺陷，表明端粒酶有助于IRF-4调节细胞增殖。 IRF-4和IRF-8诱导端粒酶与TERT启动子的激活有关。 IRF-4在体内与TERT核心启动子区域中的干扰素应答刺激元件和伽马干扰素激活的序列复合结合位点结合。此外，Sp1，Sp3，USF-1，USF-2和c-Myc与TERT启动子的结合在表达IRF-4的细胞中增加。在激活TERT启动子时，IRF-4（而非IRF-8）与Sp1和Sp3协同合作。总而言之，这些结果表明，IRF-4和IRF-8这两个淋巴样细胞特异性转录因子通过激活免疫细胞中的TERT转录来增加端粒酶活性。

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