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Biochem Biophys Res Commun. 2012 Feb 24;418(4):786-91. doi: 10.1016/j.bbrc.2012.01.104. Epub 2012 Jan 28.

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

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  • 1Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, MA 02215, United States.

Abstract

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 'master regulator' 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.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22310711
[PubMed - indexed for MEDLINE]
PMCID:
PMC3289513
Free PMC Article

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