Quality Control

How cells take out the trash

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Science  22 Jul 2016:
Vol. 353, Issue 6297, pp. 360-361
DOI: 10.1126/science.353.6297.360-b

Misfolded proteins are generally sequestered and then degraded by one of a number of quality-control pathways within cells. Lysosomal enzymes in the endolysosomal system or proteasomes in the cytosol can do this. Lee et al. describe a rather unexpected way that some cells, when subjected to proteasomal insufficiency, deal with misfolded cytosolic proteins: They excrete them using an unconventional secretory pathway. The pathway involves an endoplasmic reticulum (ER)–associated deubiquitination enzyme, USP19. Somehow USP19 recognizes misfolded cytosolic proteins and delivers them to ER-associated endosomes, which then seem to spit out the aberrant proteins into the medium. How important or widespread this pathway is in normal physiology or disease remains to be seen.

Nat. Cell Biol. 18, 765 (2016).

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