The paracaspase MALT1 is essential for the activation of NF-κB in response to T cell receptor(TCR)stimula-tion.It recruits downstream TRAF6 and activates the E3 ligase activity of TRAF6 to polyubiquitinate several targets,which ultimately leads to NF-κB activation.Here we identified ubiquitin-specific protease 2a(USP2a)as a MALT1-associated protein by biochemical affinity purification.Endogenous USP2a constitutively interacted with TRAF6,but dynamically interacted with MALT1 and CARMA1 in a stimulation-dependent man-ner.RNA interference(RNAi)-mediated silencing of USP2a attenuated TCR-induced NF-κB activation and production of interleukin-2(IL-2).In addition,the ubiq-uitination of MALT1 and TRAF6 were both suppressed by USP2a knockdown.By knockdown and reconstitu-tion assays,we found that USP2a mediated the interac-tion between MALT1 and TRAF6 in a catalytic activ-ity-dependent manner.Furthermore,USP2a deSUMOy-lated TRAF6.Our findings implicate that USP2a plays an important role in TCR signaling by deSUMOylating TRAF6 and mediating TRAF6-MALT1 interaction.
Certain carbohydrate antigens of malignantly trans- formed cells have been identified as markers for the onset of can- cer and have become targets for the development of anticancer vaccine therapies. For tumor antigens, many carbohydrate antigens belong to T-independent （TI） antigens. Carbohydrate conjugated to protein carriers can switch TI antigen to a T-dependent （TD） anti- gen. Attempts to add an innate immune response element （such as Toll-like receptor ligand） to carbohydrate TI-antigens have also been studied. Glycosylation inhibitors or small interfering RNA have also been used for antitumor and/or antiviral agents. This review aims at describing the vast spectrum of tumor carbohydrate antigens and strategies to develop cancer vaccines and drugs.
LIU MinPAN QinLUO FenglingMEYERS CraigZHANG Xiao-Lian
In response to viral infection, RIG-I-like RNA helicases detect viral RNA and signal through the mitochondrial adapter protein VISA. VISA activation leads to rapid activation of transcription factors IRF3 and NF-κB, which collaborate to induce transcription of type I interferon (IFN) genes and cellular antiviral response. It has been demonstrated that VISA is activated by forming prion-like aggregates. However, how this process is regulated remains unknown. Here we show that overexpression of HSC71 resulted in potent inhibition of virus-triggered transcription of IFNB1 gene and cellular antiviral response. Consistently, knockdown of HSC71 had opposite effects. HSC71 interacted with VISA, and negatively regulated virus-triggered VISA aggregation. These findings suggest that HSC71 functions as a check against VISA-mediated antiviral response.
Zhigang LiuShu-Wen WuCao-Qi LeiQian ZhouShu LiHong-Bing ShuYan-Yi Wang
A series of neamine-heterocycle conjugates were designed and synthesized. All new compounds displayed more potent inhibitory effect on HIV replication than neamine, among them two compounds displayed stronger anti-HIV activity than neomycin B. The results suggested that it might be a promising approach to modify neamine for the discovery of new anti-HIV agents.
Ri-Bai YanYan-Fen WuJun LiuXiao-Lian ZhangXin-Shan Ye
