A newly identified interaction between nucleolar NPM1/B23 and the HTLV-I basic leucine zipper factor in HTLV-1 infected cells.

A newly identified interaction between nucleolar NPM1/B23 and the HTLV-I basic leucine zipper factor in HTLV-1 infected cells.
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新发现的 HTLV-1 感染细胞中核仁 NPM1/B23 与 HTLV-I 碱性亮氨酸拉链因子之间的相互作用

DOI:
10.3389/fmicb.2022.988944
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发表时间:
2022
影响因子:
5.2
通讯作者:
--
中科院分区:
生物学2区
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--
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人类T细胞白血病病毒1型是HTLV-1相关脊髓病/热带痉挛性下肢轻瘫和成人T细胞白血病淋巴瘤(ATL)的病原体。HTLV-1碱性亮氨酸拉链因子(HBZ)与这种病毒的致癌特性有关,尽管确切的机制尚不清楚。在这项研究中,我们确定了核磷蛋白(NPM 1/B23)作为HBZ的一个新的相互作用伙伴。我们发现sHBZ和丰度较低的uHBZ亚型与感染细胞和HTLV-1阳性患者细胞中的核仁NPM1/B23相互作用,而不像相关的非致白血病HTLV-2,-3和-4病毒的等效反义蛋白。我们进一步证明sHBZ与NPM1/B23的结合对RNase敏感。有趣的是,sHBZ被证明与其自身的RNA相互作用。通过siRNA和过表达实验,我们进一步提供证据表明NPM1/B23对病毒基因表达具有负作用,对细胞转化具有潜在影响。因此,我们的研究结果提供了一个新的见解HBZ结合伙伴在细胞定位和细胞增殖的潜在功能,并应导致更好地了解HBZ和ATL发展之间的联系。
Human T-cell leukemia virus type 1 is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia-lymphoma (ATL). The HTLV-1 basic leucine zipper factor (HBZ) has been associated to the cancer-inducing properties of this virus, although the exact mechanism is unknown. In this study, we identified nucleophosmin (NPM1/B23) as a new interaction partner of HBZ. We show that sHBZ and the less abundant uHBZ isoform interact with nucleolar NPM1/B23 in infected cells and HTLV-1 positive patient cells, unlike equivalent antisense proteins of related non-leukemogenic HTLV-2, −3 and-4 viruses. We further demonstrate that sHBZ association to NPM1/B23 is sensitive to RNase. Interestingly, sHBZ was shown to interact with its own RNA. Through siRNA and overexpression experiments, we further provide evidence that NPM1/B23 acts negatively on viral gene expression with potential impact on cell transformation. Our results hence provide a new insight over HBZ-binding partners in relation to cellular localization and potential function on cell proliferation and should lead to a better understanding of the link between HBZ and ATL development.
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