The nucleotide-binding domain of NLRC5 is critical for nuclear import and transactivation activity

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• 作者：Torsten B. Meissner^a ; ^b ; ¹ ; Amy Li^a ; ¹ ; Yuen-Joyce Liu^a ; Etienne Gagnon^a ; ^c ; Koichi S. Kobayashi^a ; ^b ; ^{Koichi_Kobayashi@dfci.harvard.edu}
• 关键词：NLR proteins ; nucleotide-binding domain (NBD) leucine-rich repeat (LRR) containing proteins ; CIITA ; MHC class II transactivator ; 尾2M ; 尾2-microglobulin ; NLS ; nuclear localization signal ; RFX ; regulatory factor X ; ATF1 ; activating transcription factor 1
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：24 February, 2012
• 卷：418
• 期：4
• 页码：786-791
• 文件大小：845 K

摘要

Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. A member of the NLR (nucleotide-binding domain, leucine-rich repeat) protein family, NLRC5, has recently been identified as a transcriptional regulator of MHC class I and related genes. While a 鈥榤aster regulator鈥?of MHC class II genes, CIITA, has long been known, NLRC5 specifically associates with and transactivates the proximal promoters of MHC class I genes. In this study, we analyzed the molecular requirements of NLRC5 nuclear import and transactivation activity. We show that NLRC5-mediated MHC class I gene induction requires an intact nuclear localization signal and nuclear distribution of NLRC5. In addition, we find that the nucleotide-binding domain (NBD) of NLRC5 is critical not only for nuclear translocation but also for the transactivation of MHC class I genes. Changing the cellular localization of NLRC5 is likely to immediately impact MHC class I expression as well as MHC class I-mediated antigen presentation. NLRC5 may thus provide a promising target for the modulation of MHC class I antigen presentation, especially in the setting of transplant medicine.