Stabilization of RNT-1 protein, runt-related transcription factor (RUNX) protein homolog of Caenorhabditis elegans, by oxidative stress through mitogen-activated protein kinase pathway.
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.
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.
Kiho
K
Lee
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.
Jiwon
J
Shim
Department of Biochemistry, College of Life Science and Technology, Yonsei University, Seoul 120-749, South Korea.
Jaebum
J
Bae
Department of Biochemistry, College of Life Science and Technology, Yonsei University, Seoul 120-749, South Korea.
Young-Joon
YJ
Kim
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. Electronic address: elegans@snu.ac.kr.
Junho
J
Lee
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D050657:Core Binding Factor alpha Subunits; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D055550:Protein Stability; D059748:Proteolysis; D036122:Receptor, EphA4 / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D050657:Core Binding Factor alpha Subunits; C493287:RNT-1 protein, C elegans; D014157:Transcription Factors; D036122:Receptor, EphA4; D054637:Dual-Specificity Phosphatases; C501201:VHP-1 protein, C elegans