Distinguishing between retention signals and degrons acting in ERAD
Author:
Shapira Ilana1, Charuvi Dana1, Elkabetz Yechiel1, Hirschberg Koret2, Bar-Nun Shoshana1
Affiliation:
1. Department of Biochemistry, George S. Wise Faculty of Life Sciences, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 2. Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Abstract
Endoplasmic reticulum-associated degradation (ERAD) eliminates aberrant proteins from the secretory pathway. Such proteins are retained in the endoplasmic reticulum and targeted for degradation by the ubiquitin-proteasome system. Cis-acting motifs can function in ERAD as retention signals, preventing vesicular export from the endoplasmic reticulum, or as degrons, targeting proteins for degradation. Here, we show that μstp, the C-terminal 20-residue tailpiece of the secretory IgM μs heavy chain, functions both as a portable retention signal and as an ERAD degron. Retention of μstp fusions of secreted versions of thyroid peroxidase and yellow fluorescent protein in the endoplasmic reticulum requires the presence of the penultimate cysteine of μstp. In its role as a portable degron, the μstp targets the retained proteins for ERAD but does not serve as an obligatory ubiquitin-conjugation site. Abolishing μstp glycosylation accelerates the degradation of both μstpCys-fused substrates, yet absence of the N-glycan eliminates the requirement for the penultimate cysteine in the retention and degradation of the unglycosylated yellow fluorescent protein. Hence, the dual role played by the μstpCys motif as a retention signal and as a degron can be attributed to distinct elements within this sequence.
Publisher
The Company of Biologists
Reference58 articles.
1. Allen, M. D., Buchberger, A. and Bycroft, M. (2006). The PUB domain functions as a p97 binding module in human peptide N-glycanase. J. Biol. Chem.281, 25502-25508. 2. Amitay, R., Bar-Nun, S., Haimovich, J., Rabinovich, E. and Shachar, I. (1991). Post-translational regulation of IgM expression in B lymphocytes. J. Biol. Chem.266, 12568-12573. 3. Amitay, R., Shachar, I., Rabinovich, E., Haimovich, J. and Bar-Nun, S. (1992). Degradation of secretory IgM in B lymphocytes occurs in a post-endoplasmic reticulum compartment and is mediated by a cysteine protease. J. Biol. Chem.267, 20694-20700. 4. Anelli, T., Alessio, M., Mezghrani, A., Simmen, T., Talamo, F., Bachi, A. and Sitia, R. (2002). ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. EMBO J.21, 835-844. 5. Anelli, T., Alessio, M., Bachi, A., Bergamelli, L., Bertoli, G., Camerini, S., Mezghrani, A., Ruffato, E., Simmen, T. and Sitia, R. (2003). Thiol-mediated protein retention in the endoplasmic reticulum: the role of ERp44. EMBO J.22, 5015-5022.
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