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The ubiquitylation machinery of the endoplasmic reticulum

Abstract

As proteins travel through the endoplasmic reticulum (ER), a quality-control system retains newly synthesized polypeptides and supports their maturation. Only properly folded proteins are released to their designated destinations. Proteins that cannot mature are left to accumulate, impairing the function of the ER. To maintain homeostasis, the protein-quality-control system singles out aberrant polypeptides and delivers them to the cytosol, where they are destroyed by the proteasome. The importance of this pathway is evident from the growing list of pathologies associated with quality-control defects in the ER.

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Figure 1: Protein degradation at the endoplasmic reticulum (ER).
Figure 2: Mechanism of protein degradation in yeast and mammalian cells.
Figure 3: Protein homeostasis in the ER.
Figure 4: Processing of N-linked glycans in the yeast and mammalian ER.

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Acknowledgements

We thank all members of the Sommer laboratory for critical reading of the manuscript. We apologize to those authors whose work could not be cited because of space limitations. Work in T.S.'s laboratory is supported by the German Research Foundation (DFG) and the RUBICON Network of Excellence. R.G. was a fellow of the Boehringer Ingelheim Fonds. S.C.H. is the recipient of a Helmholtz PhD fellowship.

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Correspondence should be addressed to T.S. (tsommer@mdc-berlin.de).

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Hirsch, C., Gauss, R., Horn, S. et al. The ubiquitylation machinery of the endoplasmic reticulum. Nature 458, 453–460 (2009). https://doi.org/10.1038/nature07962

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