Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
J Virol. 2011 Jul;85(13):6212-9. doi: 10.1128/JVI.00079-11. Epub 2011 Apr 27.
NF-κB plays a key role in innate and acquired immunity. Its activity is regulated through intricate signaling networks. Persistent or excessive activation of NF-κB induces diseases, such as autoimmune disorders and malignant neoplasms. Infection by human T cell leukemia virus type 1 (HTLV-1) causes a fatal hematopoietic malignancy termed adult T cell leukemia (ATL). The HTLV-1 viral oncoprotein Tax functions pivotally in leukemogenesis through its potent activation of NF-κB. Recent findings suggest that protein ubiquitination is crucial for proper regulation of NF-κB signaling and for Tax activity. Here, we report that ubiquitin-specific peptidase USP20 deubiquitinates TRAF6 and Tax and suppresses interleukin 1β (IL-1β)- and Tax-induced NF-κB activation. Our results point to USP20 as a key negative regulator of Tax-induced NF-κB signaling.
NF-κB 在先天和获得性免疫中发挥关键作用。其活性通过复杂的信号网络进行调节。NF-κB 的持续或过度激活会导致自身免疫性疾病和恶性肿瘤等疾病。人类 T 细胞白血病病毒 1 型 (HTLV-1) 的感染会导致一种称为成人 T 细胞白血病 (ATL) 的致命造血恶性肿瘤。HTLV-1 病毒癌蛋白 Tax 通过其对 NF-κB 的强烈激活，在白血病发生中起着关键作用。最近的研究结果表明，蛋白质泛素化对于 NF-κB 信号的适当调节和 Tax 活性至关重要。在这里，我们报告泛素特异性肽酶 USP20 去泛素化 TRAF6 和 Tax，并抑制白细胞介素 1β (IL-1β) 和 Tax 诱导的 NF-κB 激活。我们的结果表明 USP20 是 Tax 诱导的 NF-κB 信号的关键负调节剂。
