2. Academic Validation
  3. Cul5-type Ubiquitin Ligase KLHDC1 Contributes to the Elimination of Truncated SELENOS Produced by Failed UGA/Sec Decoding

Cul5-type Ubiquitin Ligase KLHDC1 Contributes to the Elimination of Truncated SELENOS Produced by Failed UGA/Sec Decoding

  • iScience. 2020 Mar 27;23(3):100970. doi: 10.1016/j.isci.2020.100970.
Fumihiko Okumura 1,  Yuha Fujiki 2,  Nodoka Oki 2,  Kana Osaki 2,  Akihiko Nishikimi 3,  Yoshinori Fukui 4,  Kunio Nakatsukasa 5,  Takumi Kamura 6
Affiliations

Affiliations

  • 1 Department of Food and Health Sciences, International College of Arts and Sciences, Fukuoka Women's University, Fukuoka 813-8582, Japan. Electronic address: [email protected].
  • 2 Department of Food and Health Sciences, International College of Arts and Sciences, Fukuoka Women's University, Fukuoka 813-8582, Japan.
  • 3 Laboratory of Biosafety Research, National Center for Geriatrics and Gerontology, Aichi 474-8511, Japan.
  • 4 Division of Immunogenetics, Department of Immunobiology and Neuroscience and Research Center for Advanced Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
  • 5 Graduate School of Natural Sciences, Nagoya City University, Aichi 467-8501, Japan.
  • 6 Division of Biological Science, Graduate School of Science, Nagoya University, Aichi 464-8602, Japan. Electronic address: [email protected].
PMID: 32200094 DOI: 10.1016/j.isci.2020.100970
Abstract

The UGA codon signals protein translation termination, but it can also be translated into selenocysteine (Sec, U) to produce selenocysteine-containing proteins (selenoproteins) by dedicated machinery. As Sec incorporation can fail, Sec-containing longer and Sec-lacking shorter proteins co-exist. Cul2-type ubiquitin ligases were recently shown to destabilize such truncated proteins; however, which ubiquitin ligase targets truncated proteins for degradation remained unclear. We report that the Cul5-type ubiquitin ligase KLHDC1 targets truncated SELENOS, a selenoprotein, for proteasomal degradation. SELENOS is involved in endoplasmic reticulum (ER)-associated degradation, which is linked to Reactive Oxygen Species (ROS) production, and the knockdown of KLHDC1 in U2OS cells decreased ER stress-induced cell death. Knockdown of SELENOS increased the cell population with lower ROS levels. Our findings reveal that, in addition to Cul2-type ubiquitin ligases, KLHDC1 is involved in the elimination of truncated oxidoreductase-inactive SELENOS, which would be crucial for maintaining ROS levels and preventing Cancer development.

Keywords

Cancer; Cell Biology; Molecular Biology.

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