Editors' ChoiceUnfolded Protein Response

Cause and Consequence

Science's STKE  17 Apr 2001:
Vol. 2001, Issue 78, pp. tw9
DOI: 10.1126/stke.2001.78.tw9

Belden and Barlowe found that yeast deficient for the family of p24 proteins involved in trafficking cargo through the secretory pathway also secreted the yeast endoplasmic reticulum (ER) chaperone Kar2p (known as BiP in mammals). Loss of p24, loss of the ER retrieval receptor that recognizes luminal proteins with the HDEL consensus sequence, or overexpression of Kar2p activated the unfolded protein response (UPR). Furthermore, all conditions that activated the UPR also caused the secretion of Kar2p, suggesting that secretion of resident ER proteins is an indicator of the UPR. Activation of the UPR may up-regulate the expression of resident ER proteins to a point that saturates that retrieval and retention machinery, leading to the secretion of the excess up-regulated proteins, and interference with proteins involved in trafficking through the secretory pathway activates UPR.

W. J. Belden, C. Barlowe, Deletion of yeast p24 genes activates the unfolded protein response. Mol. Biol. Cell 12, 957-969 (2001). [Abstract] [Full Text]