Discovery of human breast cancer cell MCF7 heat induced proteins by LC-MS/MS

Co-translational degradation via the ubiquitin-proteasome system mediates quality control of 15 – 25% of nascent proteins, a proportion that is known to increase dramatically under proteotoxic stress conditions. Whereas the ubiquitylation machinery involved has been characterized, mechanisms coordinating the proteasomal destruction of ribosome-attached nascent proteins remain poorly defined. In pursuit of such mechanisms, we discovered dual cooperation of the HSP70 family member HSPA1 with the 26S proteasome: First, in response to proteotoxic stress, HSPA1 promotes proteasome recruitment to translating 80S ribosomes in a manner independent of nascent chain ubiquitylation. Secondly, HSPA1, in association with its cognate nucleotide exchange factor HSPH1, maintains co-translationally ubiquitylated proteins in a soluble state required for efficient proteasomal degradation.