Scholarlink

<p>Nuclear factor-κB (NF-κB) nuclear localization and gene accessibility is mediated by Ser22-phosphorylated lamin A/C (pSer22-lamin A/C). Here, we report that the intracellular bacterium <i>Orientia tsutsugamushi</i> impairs NF-κB nuclear accumulation by targeting lamin A using multiple ankyrin repeat (AR)-containing effectors (Anks). The Anks’ immunomodulatory capability requires a conserved hydrophilic α-helical peptide that binds lamin A/pSer22-lamin A and lies between the AR and PRANC (pox proteins repeats of ankyrin C-terminal) domains. <i>Orientia</i> promotes pSer22-lamin A redistribution from the lamina to the nucleoplasm. This phenotype can be recapitulated in uninfected cells by ectopically expressing Anks that carry the lamin A-binding sequence. <i>O. tsutsugamushi</i> also alters chromatin accessibility at sites regulated by lamin A, NF-κB, and the NF-κB coactivator, adapter protein 1. These findings identify a mechanism by which a pathogen synergistically modulates lamin A and chromatin accessibility to counteract NF-κB, reinforce the regulatory link between lamin A and NF-κB, and indicate that pSer22-lamin A enhances chromatin accessibility to NF-κB and its coactivators.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Orientia tsutsugamushi targets lamin A using Ank effectors and alters chromatin to inhibit NF-κB

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月11日

查看全文
  • Thomas E. Siff,
  • Paige E. Allen,
  • Haley E. Adcox,
  • Svetlana Blinova,
  • Travis J. Chiarelli,
  • Jason R. Hunt,
  • Joseph Wang,
  • David L. Armistead,
  • John S. Billingsley,
  • Nathaniel O’Bier,
  • Christofer N. Perry,
  • Kelsey N. O’Neill,
  • Richard T. Marconi,
  • Mikhail Dozmorov,
  • Andrew K. Ottens,
  • Jason A. Carlyon

摘要

Nuclear factor-κB (NF-κB) nuclear localization and gene accessibility is mediated by Ser22-phosphorylated lamin A/C (pSer22-lamin A/C). Here, we report that the intracellular bacterium Orientia tsutsugamushi impairs NF-κB nuclear accumulation by targeting lamin A using multiple ankyrin repeat (AR)-containing effectors (Anks). The Anks’ immunomodulatory capability requires a conserved hydrophilic α-helical peptide that binds lamin A/pSer22-lamin A and lies between the AR and PRANC (pox proteins repeats of ankyrin C-terminal) domains. Orientia promotes pSer22-lamin A redistribution from the lamina to the nucleoplasm. This phenotype can be recapitulated in uninfected cells by ectopically expressing Anks that carry the lamin A-binding sequence. O. tsutsugamushi also alters chromatin accessibility at sites regulated by lamin A, NF-κB, and the NF-κB coactivator, adapter protein 1. These findings identify a mechanism by which a pathogen synergistically modulates lamin A and chromatin accessibility to counteract NF-κB, reinforce the regulatory link between lamin A and NF-κB, and indicate that pSer22-lamin A enhances chromatin accessibility to NF-κB and its coactivators.