Assembly and quality control of protein phosphatase 1 holoenzyme involve Cdc48-Shp1 chaperone

• Main Authors: You-Liang Cheng, 鄭有良
• Other Authors: Rey-Huei Chen
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/51244940544590036565

博士 === 國防醫學院 === 生命科學研究所 === 103 === Protein phosphatase 1 (PP1) executes many cellular functions through association with specific regulatory proteins. We have previously shown that the nuclear accumulation of PP1 catalytic subunit, Glc7, requires Cdc48-Shp1 chaperone in the budding yeast Saccharomyces cerevisiae. In this study, I further show that the mutations in Shp1 cause misfolding of Glc7 that co-aggregates with Hsp104 and Hsp42 chaperones. The misfolded Glc7 derives from newly synthesized protein and is degraded by the proteasome. Mutation or depletion of the regulatory proteins Sds22 or Ypi1 also reduces nuclear Glc7 and causes Glc7 aggregation, indicating that Sds22 and Ypi1 are required for the maintenance of Glc7 conformation. Using substrate-trap cdc48QQ mutant, I demonstrate that Cdc48-Shp1 transiently associates with Glc7-Sds22-Ypi1. In addition, PP1-like phosphatases, Ppz2 and Ppq1, are also found in Cdc48-Shp1 complex and form foci upon Shp1 depletion. Therefore, Cdc48-Shp1 functions as a molecular chaperone for the structural integrity of PP1 complex in general and that it specifically promotes the assembly of Glc7-Sds22-Ypi1 for nuclear import.