HSP70 Isoforms Ssa1 and Ssa2 are Differentially Required in San1 Mediated Degradation

Abstract

Misfolded proteins have the propensity to aggregate and become toxic to the cell if they accumulate. To counter this detrimental burden, the eukaryotic cell has developed a variety of protein quality control (PQC) mechanisms to eliminate misfolded proteins from the cell. One mechanism is the coordination between chaperones and degradation machinery, which can help the cell rid itself of misfolded proteins. In the cytosol and endoplasmic reticulum, chaperones are often required for the degradation of misfolded proteins. In the nucleus, however, the requirement for chaperones in the degradation of nuclear localized misfolded proteins is not clear. Previously, we found that the yeast ubiquitin-protein ligase San1 ubiquitinates misfolded nuclear proteins for proteasomal degradation. It has been shown that Ssa1 and Ssa2 are the dominantly expressed isoforms of HSP70 and that they are required for the degradation of some substrates that were originally thought to be cytosolic, but were found to be nuclear localized. Here we explored the requirement for Ssa1 and Ssa2 in San1-mediated degradation and found that the involvement of the Hsp70 chaperones Ssa1 and Ssa2 is not universal, and the requirement for Ssa1 and Ssa2 correlates with substrate solubility.