A molecular portrait of the response to unfolded proteins

Abstract

Using DNA microarrays, 381 genes have been found to be induced in response to unfolded proteins. The identity of the previously characterized 208 of these, and further experiments, have revealed new details on the scope of the unfolded protein response and its connection to the degradation of proteins at the endoplasmic reticulum.

Figure 1

Unfolded proteins in the endoplasmic reticulum activate both ER-associated degradation (ERAD) and the unfolded protein response (UPR). Unfolded proteins are banished to the cytosol, by Sec61p-mediated retro-translocation, for degradation by the proteasome. Unfolded proteins also activate the ER transmembrane kinase/nuclease, Ire1p, which in conjunction with the tRNA ligase, Rlg1p, splices the HAC1 primary transcript. HAC1 mRNA passes to the cytoplasm for translation, and the newly synthesized transcription factor, Hac1p, enters the nucleus where it affects transcription of the UPR target genes. Translation of the target gene mRNAs provides proteins for secretory pathway functions and other cellular processes. The model was adapted from [20].