The Type II Hsp40 Sis1 Cooperates with Hsp70 and the E3 Ligase Ubr1 to Promote Degradation of Terminally Misfolded Cytosolic Protein

• DOI: 10.1371/journal.pone.0052099
• Publication Date: 2013-01-16T22:10:40Z
• Authors: Daniel W. Summers; Katie J. Wolfe; Hong Yu Ren; Douglas M. Cyr
• Keywords: Aggresome; Chaperone (clinical); Protein Degradation; Ubiquitin-Protein Ligases

Mechanisms for cooperation between the cytosolic Hsp70 system and ubiquitin proteasome during protein triage are not clear. Herein, we identify new mechanisms selection of misfolded proteins degradation via defining functional interactions specific Hsp70/Hsp40 pairs quality control ligases. These studies revolved around use S. cerevisiae to elucidate pathway a terminally reporter protein, short-lived GFP (slGFP). The Type I Hsp40 Ydj1 acts with suppress slGFP aggregation. In contrast, II Sis1 is required proteasomal slGFP. operate sequentially E3 ligase Ubr1 target degradation. Compromise or function leads accumulate in Triton X-100-soluble state intermediates being concentrated into perinuclear peripheral puncta. Interestingly, when activity low that puncta can be liberated from subsequently degraded. Conversely, absence Ubr1, contain relatively stable. mediates released handling centers. Pathways involve interplay Hsp40/Hsp70 chaperone pairs, PQC ligases, storage depots proteins.