Novel role of HIV-1 Nef in regulating the ubiquitination of cellular proteins.
Novel role of HIV-1 Nef in regulating the ubiquitination of cellular proteins.
复制标题
DOI：
10.3389/fcimb.2023.1106591
复制
发表时间：
2023
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
我们最近的数据表明，HIV-1 Nef 在通过调节泛素化来决定细胞蛋白质的命运方面发挥着关键作用。然而，尚不清楚哪些蛋白质在 Nef 存在的情况下被泛素化，这个问题对于理解 HIV-1 在受感染细胞中的增殖/限制策略至关重要。为了鉴定被 Nef 泛素化的细胞蛋白，我们在存在和不存在 Nef 的情况下对细胞蛋白进行了蛋白质组分析。 HEK293T 细胞中的蛋白质组学分析表明，Nef 上调了 93 种蛋白质的泛素化状态，下调了 232 种蛋白质的泛素化状态。计算分析根据分子功能、生物过程、亚细胞定位和生物途径对这些蛋白质进行分类。在这些蛋白质中，我们发现大多数分子功能涉及结合和催化活性。就生物过程而言，所鉴定的蛋白质的很大一部分与细胞和代谢过程有关。亚细胞定位分析显示大部分蛋白质定位于胞质和胞质区室，这与 HIV-1 感染期间 Nef 的已知功能和位置一致。至于生物学途径，广泛的受影响蛋白质通过多种模式来实现功能，这与未检测到的严格单一手段不同。在这些泛素化蛋白中，有 6 种被发现与 Nef 直接相互作用，其中 2 种上调，4 种下调。我们还通过直接参与泛素蛋白酶体系统 (UPS) 介导的蛋白酶体降解途径，鉴定了 14 种与蛋白质稳定性有关的蛋白质。在这些蛋白质中，我们发现六种上调，八种下调。总而言之，这些分析表明 HIV-1 Nef 通过调节泛素化来调节各种细胞蛋白的稳定性。目前正在研究指导 Nef 触发的细胞蛋白泛素化调节的分子机制。
Our recent data established that HIV-1 Nef is pivotal in determining the fate of cellular proteins by modulating ubiquitination. However, it is unknown which proteins are ubiquitinated in the presence of Nef, a question critical for understanding the proliferation/restriction strategies of HIV-1 in infected cells. To identify cellular proteins ubiquitinated by Nef, we conducted a proteomic analysis of cellular proteins in the presence and absence of Nef. Proteomic analysis in HEK293T cells indicated that 93 proteins were upregulated and 232 were downregulated in their ubiquitination status by Nef. Computational analysis classified these proteins based on molecular function, biological process, subcellular localization, and biological pathway. Of those proteins, we found a majority of molecular functions to be involved in binding and catalytic activity. With respect to biological processes, a significant portion of the proteins identified were related to cellular and metabolic processes. Subcellular localization analysis showed the bulk of proteins to be localized to the cytosol and cytosolic compartments, which is consistent with the known function and location of Nef during HIV-1 infection. As for biological pathways, the wide range of affected proteins was denoted by the multiple modes to fulfill function, as distinguished from a strictly singular means, which was not detected. Among these ubiquitinated proteins, six were found to directly interact with Nef, wherein two were upregulated and four downregulated. We also identified 14 proteins involved in protein stability through directly participating in the Ubiquitin Proteasome System (UPS)-mediated proteasomal degradation pathway. Of those proteins, we found six upregulated and eight downregulated. Taken together, these analyses indicate that HIV-1 Nef is integral to regulating the stability of various cellular proteins via modulating ubiquitination. The molecular mechanisms directing Nef-triggered regulation of cellular protein ubiquitination are currently under investigation.
泛素 E3 连接酶 c-Cbl 是 HIV-1 Nef 蛋白的宿主负调节因子。
影响因子：
5.2
作者：
Zhang HG;Guo J;Yuan Y;Zuo Y;Liu J;Zhu L;Miao Y;Chen X;Jin L;Huang F;Ren T;He J;Shi W;Wen Z;Zhu C;Zheng H;Dong C;Qian F
通讯作者：
Qian F