Involvement of DNA binding domain in the cellular stability and importin affinity of NF-κB component RelB

Masatoshi Takeiri, Kana Horie, Daisuke Takahashi, Mariko Watanabe, Ryoichi Horie, Siro Simizu, Kazuo Umezawa

研究成果: Article査読

22 被引用数 (Scopus)

抄録

NF-κB is a transcription factor for the immune activation and tissue stability, but excess activation of NF-κB often causes inflammation and cancer. An NF-κB component RelB is involved in B-cell maturation and autoimmunity. In the present research we studied the role of the RelB DNA binding domain on cellular stability and importin affinity. We prepared a RelB protein mutated at Arg141 to Ala and Tyr142 to Ala (AA mutant) having no DNA binding activity. The stability of this mutant protein was greatly reduced compared with that of the wild-type protein. We also constructed a nuclear localization signal-inactivated mutant of RelB, and found that this mutant was also unstable in the cells. Thus, RelB destabilization was caused by the loss of DNA binding possibly because of the change in cellular localization. The mutation also decreased the affinity to importin-α5 decreasing the nuclear localization. Our newly discovered NF-κB inhibitor (-)-DHMEQ binds to a specific Cys residue in RelB to inhibit DNA binding and also decreased the stability and importin affinity. These findings would indicate that the DNA binding activity of this transcription factor is a crucial for its stability and intracellular localization.

本文言語English
ページ(範囲)3053-3059
ページ数7
ジャーナルOrganic and Biomolecular Chemistry
10
15
DOI
出版ステータスPublished - 2012 4 21

ASJC Scopus subject areas

  • 生化学
  • 物理化学および理論化学
  • 有機化学

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