Viral infection kills (red) cells that have adapted to the expression of a misfolded protein (right).

Cells adjust to cope with long-term stress, according to Bridges et al. (page 395), but the adjustments make them ultrasensitive to a second stress. The timing of subsequent insults might explain the variation seen in the onset of a variety of diseases.

One disease with a highly variable age of onset is interstitial lung disease (ILD), which can be caused by mutations in the gene for the SP-C lung surfactant protein. The SP-CΔexon4 mutant version accumulates as a misfolded protein in the ER. Using this mutation to study the ER unfolded protein response (UPR), Bridges et al. discovered that cells deal with chronic stress and acute problems much differently.

Acute UPR activation causes cells to slow general translation, make more chaperones, and up-regulate the proteosome to alleviate...

The Rockefeller University Press
2006
The Rockefeller University Press
2006
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