Cross-species Analysis Reveals Evolving and Conserved Features of the Nuclear Factor κB (NF-κB) Proteins
| Autor: | Irina A. Udalova, Jiannis Ragoussis, Katrina Blazek, David Saliba, Grigory Ryzhakov, Tatsushi Muta, Ana Teixeira |
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| Rok vydání: | 2013 |
| Předmět: |
Evolution
Protein/Protein Interactions Nuclear Localization Signals Nematostella vectensis IκB Biochemistry NF-κB Conserved sequence Protein–protein interaction 03 medical and health sciences Transactivation 0302 clinical medicine Cell Signaling Species Specificity B-Cell Lymphoma 3 Protein Proto-Oncogene Proteins Animals Humans Gene Regulation 14. Life underwater Molecular Biology Transcription factor Gene 030304 developmental biology Genetics 0303 health sciences biology NF-kappa B Starlet sea anemone Promoter Cell Biology Protein/Nucleic Acid Interaction biology.organism_classification Biological Evolution Immune Sea Anemones 030220 oncology & carcinogenesis Protein Multimerization Transcription Nuclear localization sequence Transcription Factors |
| Zdroj: | The Journal of Biological Chemistry Journal of Biological Chemistry; Vol 288 |
| ISSN: | 0021-9258 |
| Popis: | Background: NF-κB regulates transcription via binding to DNA and interactions with cofactors. Results: NF-κB binding to DNA and cytosolic IκBs is conserved, whereas binding to nuclear IκBs has evolved. Conclusion: There is distinct evolutionary pressure on two NF-κB/IκB binding interfaces. Significance: The results provide inroads into IκB-specific modulation of NF-κB activity. NF-κB is a key regulator of immune gene expression in metazoans. It is currently unclear what changes occurred in NF-κB during animal evolution and what features remained conserved. To address this question, we compared the biochemical and functional properties of NF-κB proteins derived from human and the starlet sea anemone (Nematostella vectensis) in 1) a high-throughput assay of in vitro preferences for DNA sequences, 2) ChIP analysis of in vivo recruitment to the promoters of target genes, 3) a LUMIER-assisted examination of interactions with cofactors, and 4) a transactivation assay. We observed a remarkable evolutionary conservation of the DNA binding preferences of the animal NF-κB orthologs. We also show that NF-κB dimerization properties, nuclear localization signals, and binding to cytosolic IκBs are conserved. Surprisingly, the Bcl3-type nuclear IκB proteins functionally pair up only with NF-κB derived from their own species. The basis of the differential NF-κB recognition by IκB subfamilies is discussed. |
| Databáze: | OpenAIRE |
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