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Science 28 February 2003:
Vol. 299. no. 5611, pp. 1394 - 1397
DOI: 10.1126/science.1079181
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Reports

EDEM As an Acceptor of Terminally Misfolded Glycoproteins Released from Calnexin

Yukako Oda,1 Nobuko Hosokawa,12 Ikuo Wada,23* Kazuhiro Nagata12dagger

Terminally misfolded proteins in the endoplasmic reticulum (ER) are retrotranslocated to the cytoplasm and degraded by proteasomes through a mechanism known as ER-associated degradation (ERAD). EDEM, a postulated Man8B-binding protein, accelerates the degradation of misfolded proteins in the ER. Here, EDEM was shown to interact with calnexin, but not with calreticulin, through its transmembrane region. Both binding of substrates to calnexin and their release from calnexin were required for ERAD to occur. Overexpression of EDEM accelerated ERAD by promoting the release of terminally misfolded proteins from calnexin. Thus, EDEM appeared to function in the ERAD pathway by accepting substrates from calnexin.

1 Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8397, Japan.
2 Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Japan.
3 Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
*   Present address: Institute of Biomedical Sciences, Fukushima Medical University, Fukushima 960-1295, Japan.

dagger    To whom correspondence should be addressed. E-mail: nagata{at}frontier.kyoto-u.ac.jp

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