論文

査読有り 国際誌
2020年2月

Identification of novel interacting regions involving calcineurin and nuclear factor of activated T cells.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • Noriko Kitamura
  • ,
  • Mayumi Shindo
  • ,
  • Jun Ohtsuka
  • ,
  • Akira Nakamura
  • ,
  • Masaru Tanokura
  • ,
  • Takachika Hiroi
  • ,
  • Osamu Kaminuma

34
2
開始ページ
3197
終了ページ
3208
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1096/fj.201902229

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.

リンク情報
DOI
https://doi.org/10.1096/fj.201902229
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31909857

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