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Abstract：
African swine fever (ASF) is an acute, hemorrhagic, highly contagious disease in pigs caused by African swine fever virus (ASFV). Our previous study identified that the ASFV MGF300-2R protein functions as a virulence factor and found that MGF300-2R degrades IKKβ via selective autophagy. However, the E3 ubiquitin ligase responsible for IKKβ ubiquitination during autophagic degradation still remains unknown. In order to solve this problem, we first pulled down 328 proteins interacting with MGF300-2R through immunoprecipitation-mass spectrometry. Next, we analyzed and confirmed the interaction between the E3 ubiquitin ligase TRIM21 and MGF300-2R and demonstrated the catalytic role of TRIM21 in IKKβ ubiquitination. Finally, we indicated that the degradation of IKKβ by MGF300-2R was dependent on TRIM21. In summary, our results indicate TRIM21 is the E3 ubiquitin ligase involved in the degradation of IKKβ by MGF300-2R, thereby augmenting our understanding of the functions of MGF300-2R and offering insights into the rational design of live attenuated vaccines and antiviral strategies against ASF.
摘要：
非洲猪瘟（ASF）是一种急性，出血性,由非洲猪瘟病毒（ASFV）引起的猪的高度传染性疾病。我们先前的研究确定ASFVMGF300-2R蛋白作为毒力因子起作用，并发现MGF300-2R通过选择性自噬降解IKKβ。然而,在自噬降解过程中负责IKKβ泛素化的E3泛素连接酶仍然未知。为了解决这个问题,我们首先通过免疫沉淀-质谱法提取了328种与MGF300-2R相互作用的蛋白质。接下来,我们分析并证实了E3泛素连接酶TRIM21和MGF300-2R之间的相互作用，并证明了TRIM21在IKKβ泛素化中的催化作用。最后,我们表明MGF300-2R对IKKβ的降解依赖于TRIM21。总之,我们的结果表明TRIM21是参与MGF300-2R降解IKKβ的E3泛素连接酶，从而增强我们对MGF300-2R功能的理解，并提供对减毒活疫苗的合理设计和针对ASF的抗病毒策略的见解。
