發現新的蛋白質品管系統中的辨識機制

蛋白質是源自於基因的產物負責執行最重要的細胞生理功能，但是細胞時常受到環境的刺激進而引發蛋白質變異。在人類硒蛋白(Selenoprotein)中，細胞會將其信使RNA上編碼區的UGA轉譯為硒半胱胺酸(Selenocysteine)，做出全長的硒蛋白，然而在硒元素不足時，細胞可能將編碼硒半胱胺酸的UGA作為終止密碼子，做出不完整的硒蛋白。細胞如何辨識缺陷的蛋白質以控制品質，是生物學中核心的問題。我們的研究指出硒蛋白的品質控管在細胞內主要是由CRL2蛋白質複合體所負責，CRL2可說是細胞的品管大師：它不但能區別全長或因錯譯導致缺陷的硒蛋白，CRL2還能將多種缺陷蛋白貼上分解標籤，維持蛋白質體的正確性。
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Contact

Prof. Dr. Yen, Hsueh-Chi Sherry

hyen@imb.sinica.edu.tw

Original Publication

Lin, H.-C, Ho, S.-C., Chen, Y.-Y., Khoo, K.-H., Hsu., P.-H. and Yen, H.-C. S.
CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding

Science 349, 91-95 (2015) - DOI

Lin, H.-C, Yeh, C.-W., Chen, Y.-F., Lee, T.-T., Hsieh, P.-Y., Rusnac, D. V., Lin, S.-Y., Elledge, S. J., Zheng, N. and Yen, H.-C. S.
C-Terminal End-Directed Protein Elimination by CRL2 Ubiquitin Ligases

Mol Cell 70, 602-613 (2018) - DOI

Domnita-Valeria Rusnac, Lin, Hsiu-Chuan, Daniele Canzani, Karena X. Tien, Thomas R. Hinds, Ashley F. Tsue, Matthew F. Bush, Yen, Hsueh-Chi S. and Zheng, Ning
Recognition of the Diglycine C-End Degron by CRL2KLHDC2 Ubiquitin Ligase

Mol Cell 72, 813-822 (2018) - DOI

Yeh, Chi-Wei, Huang, Wei-Chieh, Hsu, Pang-Hung, Yeh, Kun-Hai, Wang, Li-Chin, Hsu, Paul Wei-Che, Lin, Hsiu-Chuan, Chen, Yi-Ning, Chen, Shu-Chuan, Yeang, Chen-Hsiang and Yen, Hsueh-Chi S.
The C-degron pathway eliminates mislocalized proteins and products of deubiquitinating enzymes

EMBO J 40, e105846 (2021) - DOI