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Stabilization of RNT-1 Protein, Runt-related Transcription Factor (RUNX) Protein Homolog of Caenorhabditis elegans, by Oxidative Stress through Mitogen-activated Protein Kinase Pathway

  作者 Lee, K; Shim, J; Bae, J; Kim, YJ; Lee, J  
  选自 期刊  Journal of Biological Chemistry;  卷期  2012年287-13;  页码  10444-10452  
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[摘要]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.

 
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