PDF(Pubmed)
Abstract：
Major histocompatibility complex (MHC) class I molecules play an essential role in regulating the adaptive immune system by presenting antigens to CD8 T cells. CITA (MHC class I transactivator), also known as NLRC5 (NLR family, CARD domain-containing 5), regulates the expression of MHC class I and essential components involved in the MHC class I antigen presentation pathway. While the critical role of the nuclear distribution of NLRC5 in its transactivation activity has been known, the regulatory mechanism to determine the nuclear localization of NLRC5 remains poorly understood. In this study, a comprehensive analysis of all domains in NLRC5 revealed that the regulatory mechanisms for nuclear import and export of NLRC5 coexist and counterbalance each other. Moreover, GCN5 (general control non-repressed 5 protein), a member of HATs (histone acetyltransferases), was found to be a key player to retain NLRC5 in the nucleus, thereby contributing to the expression of MHC class I. Therefore, the balance between import and export of NLRC5 has emerged as an additional regulatory mechanism for MHC class I transactivation, which would be a potential therapeutic target for the treatment of cancer and virus-infected diseases.
摘要：
MHC(主要组织相容性复合体)I类分子通过将抗原呈递至CD8T细胞而在调节适应性免疫系统中起重要作用。CITA（MHCI类反式激活因子），也称为NLRC5（NLR家族，包含CARD域的5），调节MHCI类和参与MHCI类抗原呈递途径的必需成分的表达。虽然NLRC5的核分布在其反式激活活性中的关键作用是已知的，确定NLRC5核定位的调节机制仍然知之甚少。在这项研究中,对NLRC5所有领域的综合分析表明，NLRC5核进出口的监管机制并存，相互抵消。此外，GCN5（一般对照非阻遏5蛋白），HAT（组蛋白乙酰转移酶）的成员，被发现是将NLRC5保留在细胞核中的关键角色，从而有助于I类MHC的表达。因此，NLRC5的进口和出口之间的平衡已经成为MHCI类反式激活的额外调节机制，这将是治疗癌症和病毒感染疾病的潜在治疗靶点。
