Abstract：
:When faced with proteotoxic stress, cells mount adaptive responses to eliminate aberrant proteins. Adaptive responses increase the expression of protein folding and degradation factors to enhance the cellular quality control machinery. However, it is unclear whether and how this augmented machinery acquires new activities during stress. Here, we uncover a regulatory cascade in budding yeast that consists of the hydrophilin protein Roq1/Yjl144w, the HtrA-type protease Ynm3/Nma111, and the ubiquitin ligase Ubr1. Various stresses stimulate ROQ1 transcription. The Roq1 protein is cleaved by Ynm3. Cleaved Roq1 interacts with Ubr1, transforming its substrate specificity. Altered substrate recognition by Ubr1 accelerates proteasomal degradation of misfolded as well as native proteins at the endoplasmic reticulum membrane and in the cytosol. We term this pathway stress-induced homeostatically regulated protein degradation (SHRED) and propose that it promotes physiological adaptation by reprogramming a key component of the quality control machinery.
journal_name
Mol Celljournal_title
Molecular cellauthors
Szoradi T,Schaeff K,Garcia-Rivera EM,Itzhak DN,Schmidt RM,Bircham PW,Leiss K,Diaz-Miyar J,Chen VK,Muzzey D,Borner GHH,Schuck Sdoi
10.1016/j.molcel.2018.04.027subject
Has Abstractpub_date
2018-06-21 00:00:00pages
1025-1037.e5issue
6eissn
1097-2765issn
1097-4164pii
S1097-2765(18)30349-6journal_volume
70pub_type
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