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Abstract：
Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma. The HTLV-1 Tax constitutively activates nuclear factor-κB (NF-κB) to promote the survival and transformation of HTLV-1-infected T cells. Despite extensive study of Tax, how Tax interacts with host factors to regulate NF-κB activation and HTLV-1-driven cell proliferation is not entirely clear. Here, we showed that overexpression of Poly (rC)-binding protein 1 (PCBP1) promoted Tax-mediated IκB kinase (IKK)-NF-κB signaling activation, whereas knockdown of PCBP1 attenuated Tax-dependent IKK-NF-κB activation. However, Tax activation of HTLV-1 long terminal repeat was unaffected by PCBP1. Furthermore, depletion of PCBP1 led to apoptosis and reduced proliferation of HTLV-1-transformed cells. Mechanistically, PCBP1 interacted and co-localized with Tax in the cytoplasm, and PCBP1 KH3 domain was indispensable for the interaction between PCBP1 and Tax. Moreover, PCBP1 facilitated the assembly of Tax/IKK complex. Collectively, our results demonstrated that PCBP1 may exert an essential effect in Tax/IKK complex combination and subsequent NF-κB activation, which provides a novel insight into the pathogenetic mechanisms of HTLV-1.
摘要：
人T细胞白血病病毒1型（HTLV-1）是成人T细胞白血病/淋巴瘤的病原体。HTLV-1Tax组成性激活核因子-κB（NF-κB）以促进HTLV-1感染的T细胞的存活和转化。尽管对税收进行了广泛的研究，Tax如何与宿主因子相互作用以调节NF-κB激活和HTLV-1驱动的细胞增殖尚不完全清楚。这里,我们发现Poly(rC)结合蛋白1(PCBP1)的过表达促进了Tax介导的IκB激酶(IKK)-NF-κB信号的激活,而PCBP1的敲除减弱了税收依赖性IKK-NF-κB的激活。然而,HTLV-1长末端重复序列的税收激活不受PCBP1的影响。此外，PCBP1的消耗导致HTLV-1转化细胞的凋亡和增殖减少。机械上,PCBP1在细胞质中与Tax相互作用并共同定位，PCBP1KH3域对于PCBP1和Tax之间的相互作用是必不可少的。此外，PCBP1促进了Tax/IKK综合体的组装。总的来说，我们的结果表明，PCBP1可能在Tax/IKK复合物组合和随后的NF-κB激活中发挥重要作用，这为HTLV-1的致病机制提供了新的见解。
