IMMUNOLOGY: Exploiting Errors

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Science  28 Apr 2000:
Vol. 288, Issue 5466, pp. 577h-577
DOI: 10.1126/science.288.5466.577h

Errors in translation of messenger RNA produce defective proteins that need to be cleared efficiently in order to avoid deleterious consequences. Protein degradation occurs via the cytosolic proteasome and produces small peptides that are suitable substrates for the transporter associated with antigen processing (TAP), which funnels peptides into the endoplasmic reticulum to be loaded onto major histocompatibility class I proteins for subsequent exposure on the cell surface. This allows immune cells to monitor which proteins are being manufactured by a cell, and hence to attack cells that appear to be expressing viral proteins.

Schubert et al. find that an astonishing 30% of all newly synthesized proteins were degraded by the proteasomal machinery, generating potential TAP substrates. Reits et al. showed that in influenza-infected cells—where protein synthesis is subverted to produce influenza virus-encoded proteins—TAP proteins were heavily laden with viral peptides. Thus, the proteasomal and antigen presentation machinery appear to be devoted largely to the processing and presentation of newly synthesized proteins, rather than proteins that have stably resided within the cytosol; this facilitates rapid immune detection of cell infection.—SMH

Nature 404, 770 (2000); Nature 404, 774 (2000).

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