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著者
Kaneko, Masayuki 大学院医歯薬保健学研究科(医) 広大研究者総覧
Iwase, Ikuko
Yamasaki, Yuki
Takai, Tomoko 大学院医歯薬保健学研究院(医)
Wu, Yan
Kanemoto, Soshi 大学院医歯薬保健学研究科(医)
Matsuhisa, Koji
Asada, Rie 大学院医歯薬保健学研究科(医)
Okuma, Yasunobu
Watanabe, Takeshi
Imaizumi, Kazunori 大学院医歯薬保健学研究科(医) 広大研究者総覧
Nomura, Yausyuki
抄録(英)
Endoplasmic reticulum (ER)-associated degradation (ERAD) is a mechanism by which unfolded proteins that accumulate in the ER are transported to the cytosol for ubiquitin–proteasome-mediated degradation. Ubiquitin ligases (E3s) are a group of enzymes responsible for substrate selectivity and ubiquitin chain formation. The purpose of this study was to identify novel E3s involved in ERAD. Thirty-seven candidate genes were selected by searches for proteins with RING-finger motifs and transmembrane regions, which are the major features of ERAD E3s. We performed gene expression profiling for the identified E3s in human and mouse tissues. Several genes were specifically or selectively expressed in both tissues; the expression of four genes (RNFT1, RNF185, CGRRF1 and RNF19B) was significantly upregulated by ER stress. To determine the involvement of the ER stress-responsive genes in ERAD, we investigated their ER localisation, in vitro autoubiquitination activity and ER stress resistance. All were partially localised to the ER, whereas CGRRF1 did not possess E3 activity. RNFT1 and RNF185, but not CGRRF1 and RNF19B, exhibited significant resistance to ER stressor in an E3 activity-dependent manner. Thus, these genes are possible candidates for ERAD E3s.
内容記述
This study was supported by Grants-in-Aid for Scientific Research (KAKENHI) 15K21706, 26460099, 24300135, 22020032, 25251014, 15K15067, 15K20001, 15K18377 and 15K19516 from the Ministry of Education, Culture, Sports, Science and Technology, Japan and also supported by the Takeda Science Foundation. We thank H. Hishigaki and Otsuka GEN Research Institute for bioinformatic analysis. We also thank M. Minami and T. Uehara for the helpful discussions. We are grateful to T. Yoshikawa, T. Ike, Y. Maeoka, Y. Wada and Z. Cao for their technical assistance. The authors would like to thank Enago (www.enago.jp) for the English language review.
掲載誌名
Scientific Reports
6巻
開始ページ
30955
出版年月日
2016-08-03
出版者
Nature Research
ISSN
2045-2322
出版者DOI
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
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application/pdf
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部局名
医歯薬保健学研究科