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Targeting proteins for degradation

Nature Chemical Biology volume 5, pages 815–822 (2009)Cite this article

An Erratum to this article was published on 01 December 2009

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Abstract

Protein degradation plays a central role in many cellular functions. Misfolded and damaged proteins are removed from the cell to avoid toxicity. The concentrations of regulatory proteins are adjusted by degradation at the appropriate time. Both foreign and native proteins are digested into small peptides as part of the adaptive immune response. In eukaryotic cells, an ATP-dependent protease called the proteasome is responsible for much of this proteolysis. Proteins are targeted for proteasomal degradation by a two-part degron, which consists of a proteasome binding signal and a degradation initiation site. Here we describe how both components contribute to the specificity of degradation.

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Figure 1: The overall structure of the eukaryotic proteasome and the bacterial ClpAP protease.

Katie Vicari

Figure 2: Mechanisms of targeting ubiquitinated proteins to the proteasome.

Katie Vicari

Figure 3: An initiation site is required for protein degradation.

Katie Vicari

Figure 4: The Cdc48/p97 targeting machine.

Katie Vicari

Figure 5: Degradation of specific subunits from larger complexes.

Katie Vicari

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Change history

  • 28 October 2009

    In the version of this article initially published, a positive competing financial interest statement was noted, where none exists. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank members of the Matouschek lab for advice and comments. The work was supported by grant R01GM64003 from the US National Institutes of Health, by grant MCB 426913 from the US National Science Foundation and by the Robert H. Lurie Comprehensive Cancer Center at Northwestern University. E.K.S. was supported by the Oncogenesis and Developmental Biology training grant T32 CA080621 from the US National Institutes of Health.

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  1. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois, USA, and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA.,

    Erin K Schrader, Kristine G Harstad & Andreas Matouschek

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  1. Erin K Schrader
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Correspondence to Andreas Matouschek.

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Schrader, E., Harstad, K. & Matouschek, A. Targeting proteins for degradation. Nat Chem Biol 5, 815–822 (2009). https://doi.org/10.1038/nchembio.250

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