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Taking a bite: proteasomal protein processing

The proteasome is a hollow cylindrical protease that contains active sites concealed within its central cavity. Proteasomes usually completely degrade substrates into small peptides, but in a few cases, degradation can yield biologically active protein fragments. Examples of this are the transcription factors NF-κB, Spt23p and Mga2p, which are generated from precursors by proteasomal processing. How distinct protein domains are spared from degradation remains a matter of debate. Here, we discuss several models and suggest a novel mechanism for proteasomal processing.

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Figure 1: Hypothetical models for proteasomal protein processing of NF-κB p105 and Spt23p p120.
Figure 2: A polypeptide loop as a possible substrate for the proteasome.

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Acknowledgements

We thank M. Groll for preparing Fig. 2, and W. Baumeister, G. DeMartino, M. Groll, T. Hoppe, R. Huber, L. Lin and A. Matouschek for discussions.

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Rape, M., Jentsch, S. Taking a bite: proteasomal protein processing. Nat Cell Biol 4, E113–E116 (2002). https://doi.org/10.1038/ncb0502-e113

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