News & Views | Published:

Making the cut: intramembrane cleavage by a rhomboid protease promotes ERAD

Nature Structural & Molecular Biology volume 19, pages 979981 (2012) | Download Citation

Endoplasmic reticulum–associated degradation (ERAD) is a cellular protein quality-control process that disposes of proteasomal substrates from the early secretory pathway. Recent work shows that the endoplasmic reticulum–resident rhomboid protease RHBDL4 facilitates ERAD by recognizing and cleaving integral membrane substrates. The work indicates that intramembrane proteolysis may have a general role in the extraction of misfolded membrane proteins from the endoplasmic reticulum.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & Nat. Rev. Mol. Cell Biol. 8, 519–529 (2007).

  2. 2.

    & Nat. Rev. Mol. Cell Biol. 9, 944–957 (2008).

  3. 3.

    , , & Biochim. Biophys. Acta 1808, 925–936 (2011).

  4. 4.

    et al. Nat. Cell Biol. 14, 93–105 (2012).

  5. 5.

    , & EMBO J. 25, 4557–4566 (2006).

  6. 6.

    , & J. Biol. Chem. 274, 2616–2624 (1999).

  7. 7.

    & J. Biol. Chem. 273, 32373–32376 (1998).

  8. 8.

    & Immunity 7, 113–122 (1997).

  9. 9.

    , , & J. Biol. Chem. 273, 22037–22043 (1998).

  10. 10.

    , & Nat. Struct. Mol. Biol. 18, 1147–1152 (2011).

  11. 11.

    , , , & Cell 145, 79–91 (2011).

  12. 12.

    Annu. Rev. Genet. 42, 191–210 (2008).

  13. 13.

    et al. Nature 441, 894–897 (2006).

  14. 14.

    et al. Mol. Cell 47, 558–569 (2012).

  15. 15.

    et al. Science 335, 229–232 (2012).

  16. 16.

    , , , & Science 335, 225–228 (2012).

  17. 17.

    et al. Nature 450, 1026–1030 (2007).

  18. 18.

    , & Structure 17, 395–405 (2009).

  19. 19.

    , , & Proc. Natl. Acad. Sci. USA 99, 12208–12213 (2002).

  20. 20.

    & Mol. Cell 11, 1425–1434 (2003).

  21. 21.

    & Biochemistry 48, 12314–12322 (2009).

  22. 22.

    Biochem. J. 425, 501–512 (2010).

Download references

Author information

Affiliations

  1. Ethan J. Greenblatt is at the Howard Hughes Medical Institute Research Laboratories, Department of Embryology, Carnegie Institution of Washington, Baltimore, Maryland, USA.

    • Ethan J Greenblatt
  2. James A. Olzmann and Ron R. Kopito are at Stanford University, Department of Biology, Stanford, California, USA.

    • James A Olzmann
    •  & Ron R Kopito

Authors

  1. Search for Ethan J Greenblatt in:

  2. Search for James A Olzmann in:

  3. Search for Ron R Kopito in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ron R Kopito.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nsmb.2398

Further reading

Newsletter Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing