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Protein degradation

Recruiting partners for destruction

Nature Reviews Molecular Cell Biology volume 6, pages 824–825 (2005)Cite this article

Although recognition of misfolded polypeptides takes place in the ER lumen, their proteolysis occurs in the cytosol, through a transport process known as dislocation. ERAD substrates are tagged by ubiquitin ligases for recognition, and dislocation occurs with the help of Cdc48, which is required to release substrates from the ER membrane. In an attempt to understand how Cdc48 is integrated into the ERAD pathway, Neuber and colleagues showed that Ubx2 links Cdc48 to ERAD. In a complementary report, Schuberth and Buchberger, who were interested in identifying the specific functions of yeast Ubx2, confirmed that Ubx2 recruits Cdc48 to the ER.

Indeed, both groups showed that Ubx2 localizes in the ER and behaves like an integral ER membrane protein in membrane-fractionation experiments. Studies that compared wild-type cells and cells lacking Ubx2, combined with immunoprecipitation experiments, provided evidence that Ubx2 not only contributes significantly to the recruitment of Cdc48 to the ER membrane and, more specifically, to proteins that are destined for degradation, but also provided the link between Cdc48 and the membrane-bound E3 ubiquitin ligases Hrd1 and Doa10. Furthermore, analysis of different types of ERAD substrates indicated that Ubx2 is involved in the turnover of substrates in both Hrd1- and Doa10-dependent ERAD pathways.

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References

ORIGINAL RESEARCH PAPERS

  1. Neuber, O. et al. Ubx2 links the Cdc48 complex to ER-associated protein degradation. Nature Cell Biol. 7, 993–998 (2005)

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  2. Schuberth, C. & Buchberger, A. Membrane-bound Ubx2 recruits Cdc48 to ubiquitin ligases and their substrates to ensure efficient ER-associated protein degradation. Nature Cell Biol. 7, 999–1006 (2005)

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FURTHER READING

  1. Meusser, B. et al. ERAD: the long road to destruction. Nature Cell Biol. 7, 766–772 (2005)

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Authors
  1. Ekat Kritikou
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Kritikou, E. Recruiting partners for destruction. Nat Rev Mol Cell Biol 6, 824–825 (2005). https://doi.org/10.1038/nrm1769

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