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Endoplasmic-reticulum-associated protein degradation inside and outside of the endoplasmic reticulum

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Summary

Newly synthesized polypeptides that enter the endomembrane system encounter a folding environment in the lumen of the endoplasmic reticulum (ER) constituted by enzymes, lectinlike proteins, and molecular chaperones. The folding process is under scrutiny of this abundant catalytic machinery, and failure of the new arrivals to assume a stable and functional conformation is met with targeting to proteolytic destruction, a process which has been termed ER-associated degradation (ERAD). In recent years it became clear that, in most cases, proteolysis appears to take place in the cytosol after retro-translocation of the substrate proteins from the ER, and to depend on the ubiquitin-proteasome pathway. On the other hand, proteolytic activities within the ER that have been widely neglected so far may also contribute to the turnover of proteins delivered to ERAD. Thus, ERAD is being deciphered as a complex process that requires communication-dependent regulated proteolytic activities within both the ER lumen and the cytosol. Here we discuss some recent findings on ERAD and their implications on possible mechanisms involved.

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Abbreviations

αlAT:

alpha-1-antitrypsin

apoB:

apolipoprotein B

BiP:

immunoglobulin-heavy-chain-binding protein

CFTR:

cystic fibrosis transmembrane conductance regulator

CPY:

carboxypeptidase Y

ER:

endoplasmic reticulum

ERAD ER:

associated degradation

HMG-CoA:

3-hydroxy-3-methylglutaryl coenzyme A

MHC:

major histocompatibility complex

PDI:

protein disulflde isomerase

TCR:

T cell antigen receptor

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  1. Department of Molecular Genetics, Biocenter Vienna, Dr.-Bohr-Gasse 9/2, A-1030, Vienna, Austria

    N. Erwin Ivessa, Claudia Kitzmüller & Maddalena de Virgilio

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  1. N. Erwin Ivessa
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  2. Claudia Kitzmüller
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  3. Maddalena de Virgilio
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Erwin Ivessa, N., Kitzmüller, C. & de Virgilio, M. Endoplasmic-reticulum-associated protein degradation inside and outside of the endoplasmic reticulum. Protoplasma 207, 16–23 (1999). https://doi.org/10.1007/BF01294709

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