Research progress on the antiviral immune regulation of ubiquitin ligase F-box family
孟祥博 1李天琪 1张彤1
扫码查看
点击上方二维码区域，可以放大扫码查看
作者信息
1. 解放军医学院,北京(100853);解放军总医院第一医学中心口腔科,北京(100853)
折叠
摘要
F-Box蛋白家族是存在于所有真核生物中的一个庞大且多样化的蛋白质家族,可根据蛋白C端二级结构的不同将其分为FBXW、FBXL、FBXO三类.F-Box蛋白可以通过与S期激酶相关蛋白1(S-phase kinase-associated protein 1,SKP1)、cullin 1(CUL1)、环盒蛋白 1(ring-box 1,Rbx1)结合形成 SCF复合体发挥E3泛素连接酶功能,可通过泛素-蛋白酶体途径或其他方式特异性识别底物蛋白,参与细胞周期调控、转录调控、细胞凋亡、细胞信号转导等生命活动.大量研究表明F-Box家族蛋白在宿主-病毒相互作用过程中发挥重要功能,作为SCF复合体的底物识别部分,可以与底物结合并使其K48泛素化后转运至蛋白酶体降解.根据降解的底物不同,F-Box家族蛋白一方面可以发挥抗病毒效果,另一方面可以被病毒利用产生免疫逃逸效果.部分F-Box蛋白可以特异性识别干扰素通路相关信号分子并通过泛素-蛋白酶体途径使其降解,从而上调或抑制干扰素信号,调节宿主相关免疫反应;一些F-Box蛋白可以识别病毒蛋白并通过泛素-蛋白酶体途径降解,抑制病毒的复制与传播;此外病毒还可以劫持F-Box蛋白以促使具有免疫功能的宿主蛋白降解,从而产生免疫逃逸效果.目前大量研究针对F-Box家族蛋白开发了数千种抑制剂,但利用F-Box蛋白进行抗病毒药物的研究鲜有报道.F-Box蛋白家族成员众多,其在病毒-宿主相互作用过程中的功能与机制仍需大量探索,并可成为开发抗病毒药物的新方向.
Abstract
The F-box protein(FBP)family is a large and diverse protein family that is present in all eukaryotes.Based on the secondary structure of the C-terminal,FBPs can be classified as FBXW,FBXL,and FBXO.FBPs can form the SCF complex by binding with S-phase kinase-associated protein 1(SKP1),cullin 1(CUL1),and ring-box 1(Rbx1),functioning as E3 ubiquitin ligase.They specifically recognize substrate proteins via the ubiquitin-proteasome pathway and participate in various biological activities,such as cell cycle regulation,transcriptional regulation,apopto-sis,and cell signaling transduction.Numerous studies have shown that FBPs play important roles in host-virus interac-tions.Being the substrate recognition component of the SCF complex,FBPs bind,ubiquitinate(at K-48),and transport substrates for proteasomal degradation.Based on the type of substrate,F-Box family proteins can either exert antiviral or proviral(immune evasive)effects.Some FBPs can specifically recognize and degrade interferon pathway-associated sig-nal molecules via the ubiquitin-proteasome pathway,thereby upregulating or inhibiting interferon signals and regulating host-related immune responses.Additionally,some FBPs can recognize and degrade viral proteins via the ubiquitin-pro-teasome pathway,thereby inhibiting viral replication and transmission.However,viruses can hijack FBPs to promote the degradation of immunogenic host proteins,resulting in immune evasion.Although several FBP-targeting inhibitors have been developed,there are limited reports on the application of FBPs in antiviral drug research.Given the large number of FBP family members,further research is required on the functions and mechanisms of FBPs in virus-host interac-tions,to provide novel directions for the development of antiviral drugs.
万方数据