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PMID: 20639463 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

NLR family member NLRC5 is a transcriptional regulator of MHC class I genes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 31 ·2010-08-03 ·Pages 13794-9

Meissner TB, Li A, Biswas A, Lee KH, Liu YJ, Bayir E, Iliopoulos D, van den Elsen PJ, Kobayashi KS

Abstract

MHC class I plays a critical role in the immune defense against viruses and tumors by presenting antigens to CD8 T cells. An NLR protein, class II transactivator (CIITA), is a key regulator of MHC class II gene expression that associates and cooperates with transcription factors in the MHC class II promoter. Although CIITA also transactivates MHC class I gene promoters, loss of CIITA in humans and mice results in the severe reduction of only MHC class II expression, suggesting that additional mechanisms regulate the expression of MHC class I. Here, we identify another member of the NLR protein family, NLRC5, as a transcriptional regulator of MHC class I genes. Similar to CIITA, NLRC5 is an IFN-gamma-inducible nuclear protein, and the expression of NLRC5 resulted in enhanced MHC class I expression in lymphoid as well as epithelial cell lines. Using chromatin immunoprecipitation and reporter gene assays, we show that NLRC5 associates with and activates the promoters of MHC class I genes. Furthermore, we show that the IFN-gamma-induced up-regulation of MHC class I requires NLRC5, because knockdown of NLRC5 specifically impaired the expression of MHC class I. In addition to MHC class I genes, NLRC5 also induced the expression of beta2-microglobulin, transporter associated with antigen processing, and large multifunctional protease, which are essential for MHC class I antigen presentation. Our results suggest that NLRC5 is a transcriptional regulator, orchestrating the concerted expression of critical components in the MHC class I pathway.

MeSH Terms
Active Transport, Cell Nucleus Amino Acid Sequence Cell Line Cell Nucleus/metabolism Gene Expression Regulation Genes, MHC Class I Humans Intracellular Signaling Peptides and Proteins/chemistry,genetics,metabolism Molecular Sequence Data Phylogeny Promoter Regions, Genetic Protein Binding RNA, Small Interfering/genetics Transcription, Genetic
Chemicals
Intracellular Signaling Peptides and Proteins NLRC5 protein, human RNA, Small Interfering
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Meissner Torsten B
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Li Amy
Biswas Amlan
Lee Kyoung-Hee
Liu Yuen-Joyce
Bayir Erkan
Iliopoulos Dimitrios
van den Elsen Peter J
Kobayashi Koichi S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1008684107
Published
2010-08-03
Epub
2010-00-16
Pages
13794-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2922274
Subset
IM
Grants
NIDDK NIH HHS · R01 DK074738 · United States
NIDDK NIH HHS · R01 DK074738-05 · United States
Databases
GEO
GSE22064
External Links
PubMed source DOI: 10.1073/pnas.1008684107 PMC Full Text View journal details
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