曹雪涛课题组在《Nat Immunol》 杂志发表研究论文“K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8+ T cell activation （2015）”。

      为确定E3泛素连接酶Nrdp1在T细胞介导自身免疫疾病中的作用，中国医学科学院基础医学研究所，“医学分子生物学国家重点实验室”的曹雪涛课题组揭示了两种重要的翻译后修饰在免疫信号转导通路中的交叉调控和相互制约方式，这种新型调控模式也有助于其他生命科学领域的研究。所发现的抑制Nrdp1的表达促进CD8+T细胞的抗感染和抗肿瘤活性在未来的细胞免疫治疗领域也具有极大的应用价值。

      【摘要】：The key molecular mechanisms that control signaling via T cell antigen receptors (TCRs) remain to be fully elucidated. Here we found that Nrdp1, a ring finger-type E3 ligase, mediated Lys33 (K33)-linked polyubiquitination of the signaling kinase Zap70 and promoted the dephosphorylation of Zap70 by the acidic phosphatase-like proteins Sts1 and Sts2 and thereby terminated early TCR signaling in CD8(+) T cells. Nrdp1 deficiency significantly promoted the activation of naive CD8(+) T cells but not that of naive CD4(+) T cells after engagement of the TCR. Nrdp1 interacted with Zap70 and with Sts1 and Sts2 and connected K33 linkage of Zap70 to Sts1- and Sts2-mediated dephosphorylation. Our study suggests that Nrdp1 terminates early TCR signaling by inactivating Zap70 and provides new mechanistic insights into the non-proteolytic regulation of TCR signaling by E3 ligases.

      相关结果已发表于《Nat Immunol》 杂志（2015，16(12):1253-62.），其作者为曹雪涛课题组博士研究生杨明金，重点室曹雪涛教授是本文的通讯作者。该研究工作得到了以下基金的支持：National Basic Research Program of China(2013CB530502 and 2012CB518900), and the National Natural Science Foundation of China (81123006, 31300718, 31370864,and 81422037)。