title: Identification of substrates of F-box protein involved in methylmercury toxicity in yeast cells.
abstract: We previously reported that some of the substrate proteins recognized by Hrt3 or Ucc1, a component of Skp1/Cdc53/F-box protein ubiquitin ligase, may include proteins that are involved in the methylmercury toxicity and degraded by the proteasome. In this study, we found that Dld3 and Grs1 bound to Hrt3 and that Eno2 bound to Ucc1 using a yeast two-hybrid screening. We demonstrated that Dld3 and Grs1 are substrates that are ubiquitinated by Hrt3, and Eno2 is a substrate that is ubiquitinated by Ucc1. Moreover, any yeast showing overexpression of Dld3, Grs1, and Eno2 demonstrated higher methylmercury sensitivity. This indicates that Hrt3 and Ucc1 are involved in alleviating the methylmercury toxicity by promoting proteasomal degradation through the ubiquitination of Dld3, Grs1, and Eno2.
authors: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan; Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan.
authors: Jin-Yong
authors: JY
authors: Lee
authors: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors: Yosuke
authors: Y
authors: Ishida
authors: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan; Department of Microbiology, Tohoku Pharmaceutical University, Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors: Shusuke
authors: S
authors: Kuge
authors: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors: Akira
authors: A
authors: Naganuma
authors: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan. Electronic address: gwhwang@m.tohoku.ac.jp.
authors: Gi-Wook
authors: GW
authors: Hwang
mesh_terms: D044783:F-Box Proteins / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008767:Methylmercury Compounds / Q000633:toxicity*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D044783:F-Box Proteins; D008767:Methylmercury Compounds; D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex
keywords: F-box protein; Methylmercury; Toxicity; Ubiquitination