Cul5-type Ubiquitin Ligase KLHDC1 Contributes to the Elimination of Truncated SELENOS Produced by Failed UGA/Sec Decoding
Fumihiko Okumura,
Yuha Fujiki,
Nodoka Oki,
Kana Osaki,
Akihiko Nishikimi,
Yoshinori Fukui,
Kunio Nakatsukasa,
Takumi Kamura
Affiliations
Fumihiko Okumura
Department of Food and Health Sciences, International College of Arts and Sciences, Fukuoka Women's University, Fukuoka 813-8582, Japan; Corresponding author
Yuha Fujiki
Department of Food and Health Sciences, International College of Arts and Sciences, Fukuoka Women's University, Fukuoka 813-8582, Japan
Nodoka Oki
Department of Food and Health Sciences, International College of Arts and Sciences, Fukuoka Women's University, Fukuoka 813-8582, Japan
Kana Osaki
Department of Food and Health Sciences, International College of Arts and Sciences, Fukuoka Women's University, Fukuoka 813-8582, Japan
Akihiko Nishikimi
Laboratory of Biosafety Research, National Center for Geriatrics and Gerontology, Aichi 474-8511, Japan
Yoshinori Fukui
Division of Immunogenetics, Department of Immunobiology and Neuroscience and Research Center for Advanced Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
Kunio Nakatsukasa
Graduate School of Natural Sciences, Nagoya City University, Aichi 467-8501, Japan
Takumi Kamura
Division of Biological Science, Graduate School of Science, Nagoya University, Aichi 464-8602, Japan; Corresponding author
Summary: 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. : Molecular Biology; Cell Biology; Cancer Subject Areas: Molecular Biology, Cell Biology, Cancer
