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A genomic screen identifies Dsk2p and Rad23p as essential components of ER‐associated degradation
Author(s) -
Medicherla Balasubrahmanyam,
Kostova Zlatka,
Schaefer Antje,
Wolf Dieter H
Publication year - 2004
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400164
Subject(s) - endoplasmic reticulum associated protein degradation , endoplasmic reticulum , proteasome , microbiology and biotechnology , protein degradation , ubiquitin , cytoplasm , mutant , biology , chemistry , biochemistry , unfolded protein response , gene
We developed a growth test to screen for yeast mutants defective in endoplasmic reticulum (ER) quality control and associated protein degradation (ERAD) using the membrane protein CTL * , a chimeric derivative of the classical ER degradation substrate CPY * . In a genomic screen of ∼5,000 viable yeast deletion mutants, we identified genes necessary for ER quality control and degradation. Among the new gene products, we identified Dsk2p and Rad23p. We show that these two proteins are probably delivery factors for ubiquitinated ER substrates to the proteasome, following their removal from the membrane via the Cdc48–Ufd1–Npl4p complex. In contrast to the ERAD substrate CTG * , proteasomal degradation of a cytosolic CPY * –GFP fusion is not dependent on Dsk2p and Rad23p, indicating pathway specificity for both proteins. We propose that, in certain degradation pathways, Dsk2p, Rad23p and the trimeric Cdc48 complex function together in the delivery of ubiquitinated proteins to the proteasome, avoiding malfolded protein aggregates in the cytoplasm.