Identification of novel interacting regions involving calcineurin and nuclear factor of activated T cells
| Autor: | Akira Nakamura, Mayumi Shindo, Masaru Tanokura, Osamu Kaminuma, Jun Ohtsuka, Noriko Kitamura, Takachika Hiroi |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Gene isoform Immunoprecipitation Protein subunit Biochemistry Cell Line 03 medical and health sciences Jurkat Cells 0302 clinical medicine Cricetulus NFAT5 Transcription (biology) Cricetinae Genetics Animals Humans Molecular Biology Binding Sites integumentary system NFATC Transcription Factors Chemistry Calcineurin NFAT Cell biology Molecular Docking Simulation 030104 developmental biology Ectopic expression 030217 neurology & neurosurgery Biotechnology Protein Binding |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(2) |
| ISSN: | 1530-6860 |
| Popis: | Nuclear factor of activated T cells (NFAT) leads to the transcription of diverse inducible genes involved in many biological processes; therefore, aberrant NFAT expression is responsible for the development and exacerbation of various disorders. Since five isoforms of NFAT (NFATc1-c4, NFAT5) exhibit distinct and overlapping functions, selective control of a part, but not all, of NFAT family members is desirable. By comparing the binding activity of each NFATc1-c4 with its regulatory enzyme, calcineurin (CN), using a quantitative immunoprecipitation assay, we found a new CN-binding region (CNBR) selectively functioning in NFATc1 and NFATc4. This region, termed CNBR3, is located between two preexisting CNBR1 and CNBR2, within the Ca2+ regulatory domain. The nuclear translocation of NFATc1 but not NFATc2 in T cells was suppressed by ectopic expression of CNBR3 and, accordingly, NFATc1-dependent cytokine expression was downregulated. Through competition assays using NFATc1-derived partial peptides and mass spectrometry with photoaffinity technology, we identified 18 amino acids in NFATc1 (Arg258 to Pro275 ) and 13 amino acids in CN catalytic subunit (CNA) (Asn77 to Gly89 ) responsible for CNA/CNBR3 binding in which Cys263 and Asp82 , respectively, played crucial roles. The possible selective regulation of NFAT-mediated biological processes by targeting this new CN/NFAT-binding region is suggested. |
| Databáze: | OpenAIRE |
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