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- Title
Ssz1 Restores Endoplasmic Reticulum-Associated Protein Degradation in Cells Expressing Defective Cdc48-Ufd1-Npl4 Complex by Upregulating Cdc48.
- Authors
Bosis, Eran; Salomon, Dor; Ohayon, Orit; Sivan, Gilad; Bar-Nun, Shoshana; Rabinovich, Efrat
- Abstract
The endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway eliminates aberrant proteins from the ER. The key role of Cdc48p-Ufd1p-Npl4p is indicated by impaired ERAD in Saccharomyces cerevisiae with mutations in any of this complex's genes. We identified SSZ1 in genetic screens for cdc48-10 suppressors and show that it upregulates Cdc48p via the pleiotropic drug resistance (PDR) network. A pSSZ1 plasmid restored impaired ERAD-M of 6myc-Hmg2 in cdc48-10, ufd1-2, and npl4-1, while SSZ1 deletion had no effect. Ssz1p activates Pdr1p, the PDR master regulator. Indeed, plasmids of PDR1 or its target gene RPN4 increased cdc48-10p levels and restored ERAD-M in cdc48-10. Rpn4p regulates transcription of proteasome subunits and CDC48, thus RPN4 deletion abolished ERAD. However, the diminished proteasome level in Δrpn4 was sufficient for degrading a cytosolic substrate, whereas the impaired ERAD-M was the result of diminished Cdc48p and was restored by expression of pCDC48. The corrected ERAD-M in the hypomorphic strains of the Cdc48 partners ufd1-2 and npl4-1 by the pCDC48 plasmid, and in cdc48-10 cells by the pcdc48-10 plasmid, combined with the finding that neither pSSZ1 nor pcdc48-10 restored ERAD-L of CPY*-HA, support our conclusion that Ssz1p suppressing effects is brought about by upregulating Cdc48p.
- Subjects
ENDOPLASMIC reticulum; PROTEINS; SACCHAROMYCES cerevisiae; GENETIC mutation; GENETIC testing; MULTIDRUG resistance
- Publication
Genetics, 2010, Vol 184, Issue 3, p695
- ISSN
0016-6731
- Publication type
Article
- DOI
10.1534/genetics.109.111419