Research Center for Cellulomics, Department of Biological Sciences, World Class University (WCU) Department of Biophysics and Chemical Biology, Seoul National University, Seoul, 151-742, South Korea and.
Department of Biochemistry, College of Life Science and Technology, Yonsei University, Seoul 120-749, South Korea.
J Biol Chem. 2012 Mar 23;287(13):10444-10452. doi: 10.1074/jbc.M111.314146. Epub 2012 Feb 3.
RUNX proteins are evolutionarily conserved transcription factors known to be involved in various developmental processes. Here we report a new role for a RUNX protein: a role in stress response. We show that RNT-1, the Caenorhabditis elegans RUNX homolog, is constantly produced and degraded by the ubiquitination-proteasome pathway in the intestine of the nematode. RNT-1 was rapidly stabilized by oxidative stress, and the rnt-1-mutant animals were more sensitive to oxidative stress, indicating that rapid RNT-1 stabilization is a defense response against the oxidative stress. The MAP kinase pathway is required for RNT-1 stabilization, and RNT-1 was phosphorylated by SEK-1/PMK-1 in vitro. ChIP-sequencing analysis revealed a feedback loop mechanism of the MAP kinase pathway by the VHP-1 phosphatase in the RNT-1-mediated oxidative stress response. We propose that rnt-1 is regulated at the protein level for its role in the immediate response to environmental challenges in the intestine.
RUNX 蛋白是进化上保守的转录因子，已知参与各种发育过程。在这里，我们报告了 RUNX 蛋白的一个新作用：在应激反应中的作用。我们表明，秀丽隐杆线虫的 RUNX 同源物 RNT-1 通过泛素蛋白酶体途径在线虫的肠道中不断被产生和降解。RNT-1 被氧化应激迅速稳定，而 rnt-1 突变体动物对氧化应激更敏感，表明快速稳定 RNT-1 是一种针对氧化应激的防御反应。MAP 激酶途径是 RNT-1 稳定所必需的，并且 RNT-1 在体外被 SEK-1/PMK-1 磷酸化。ChIP-seq 分析揭示了在 RNT-1 介导的氧化应激反应中 VHP-1 磷酸酶通过 MAP 激酶途径的反馈环机制。我们提出 rnt-1 在蛋白质水平上受到调节，以在肠道中对环境挑战做出即时反应。
