CIITA Leucine-Rich Repeats Control Nuclear Localization, In Vivo Recruitment to the Major Histocompatibility Complex (MHC) Class II Enhanceosome, and MHC Class II Gene Transactivation
| Autor: | Christian Janzen, C. Kammerbauer, Krzysztof Masternak, Walter Reith, Viktor Steimle, Sandra B. Hake |
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| Rok vydání: | 2000 |
| Předmět: |
Cell Extracts
RFXANK Nuclear Localization Signals ddc:616.07 MHC Class II Gene Transactivation Tumor Cells Cultured Promoter Regions Genetic Genes MHC Class II/ genetics Genetics DNA-Binding Proteins/metabolism biology Nuclear Proteins Chromatin DNA-Binding Proteins Trans-Activators/chemistry/genetics/ metabolism Enhancer Elements Genetic Phenotype Protein Binding Repetitive Sequences Amino Acid Transcriptional Activation Mutation/genetics Genes MHC Class II Molecular Sequence Data Active Transport Cell Nucleus Regulatory Factor X Transcription Factors chemical and pharmacologic phenomena Major histocompatibility complex Models Biological Enhanceosome Leucine CIITA Humans Amino Acid Sequence Molecular Biology Transcriptional Regulation Cell Nucleus Chromatin/genetics/metabolism Cytoplasmic Structures/genetics/ metabolism MHC class II Histocompatibility Antigens Class II/ metabolism Enhancer Elements Genetic/genetics Histocompatibility Antigens Class II Cell Biology Precipitin Tests Mutation Cell Nucleus/metabolism Trans-Activators biology.protein Cytoplasmic Structures Sequence Alignment RFX5 Leucine/genetics/ metabolism |
| Zdroj: | Molecular and Cellular Biology, Vol. 20, No 20 (2000) pp. 7716-7725 |
| ISSN: | 1098-5549 0270-7306 |
| DOI: | 10.1128/mcb.20.20.7716-7725.2000 |
| Popis: | The major histocompatibility complex (MHC) class II transactivator CIITA plays a pivotal role in the control of the cellular immune response through the quantitative regulation of MHC class II expression. We have analyzed a region of CIITA with similarity to leucine-rich repeats (LRRs). CIITA LRR alanine mutations abolish both the transactivation capacity of full-length CIITA and the dominant-negative phenotype of CIITA mutants with N-terminal deletions. We demonstrate direct interaction of CIITA with the MHC class II promoter binding protein RFX5 and could also detect novel interactions with RFXANK, NF-YB, and -YC. However, none of these interactions is influenced by CIITA LRR mutagenesis. On the other hand, chromatin immunoprecipitation shows that in vivo binding of CIITA to the MHC class II promoter is dependent on LRR integrity. LRR mutations lead to an impaired nuclear localization of CIITA, indicating that a major function of the CIITA LRRs is in nucleocytoplasmic translocation. There is, however, evidence that the CIITA LRRs are also involved more directly in MHC class II gene transactivation. CIITA interacts with a novel protein of 33 kDa in a manner sensitive to LRR mutagenesis. CIITA is therefore imported into the nucleus by an LRR-dependent mechanism, where it activates transcription through multiple protein-protein interactions with the MHC class II promoter binding complex. |
| Databáze: | OpenAIRE |
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