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Cleaning up in the endoplasmic reticulum: ubiquitin in charge

Nature Structural & Molecular Biology volume 21, pages 325–335 (2014)Cite this article

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Abstract

The eukaryotic endoplasmic reticulum (ER) maintains protein homeostasis by eliminating unwanted proteins through the evolutionarily conserved ER-associated degradation (ERAD) pathway. During ERAD, maturation-defective and surplus polypeptides are evicted from the ER lumen and/or lipid bilayer through the process of retrotranslocation and ultimately degraded by the proteasome. An integral facet of the ERAD mechanism is the ubiquitin system, composed of the ubiquitin modifier and the factors for assembling, processing and binding ubiquitin chains on conjugated substrates. Beyond simply marking polypeptides for degradation, the ubiquitin system is functionally intertwined with retrotranslocation machinery to transport polypeptides across the ER membrane.

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Figure 1: Distinct modes of retrotranslocation.
Figure 2: Modular organization of the mammalian ERAD system.

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Acknowledgements

We thank J. Schulz, E. Fenech, K. Bryon-Dodd (University of Oxford) and J. Olzmann (University of California, Berkeley) for critical reading of the manuscript. Research in the laboratory of Y.Y. is supported by the intramural research program of the NIDDK, US National Institutes of Health. J.C.C. is supported by funding from the Ludwig Institute for Cancer Research and the UK Medical Research Council.

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  1. john.christianson@ludwig.ox.ac.uk

  2. yihongy@mail.nih.gov

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  1. Ludwig Institute for Cancer Research, University of Oxford, Oxford, UK

    John C Christianson & John C Christianson

  2. Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Yihong Ye & Yihong Ye

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Christianson, J., Ye, Y. Cleaning up in the endoplasmic reticulum: ubiquitin in charge. Nat Struct Mol Biol 21, 325–335 (2014). https://doi.org/10.1038/nsmb.2793

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