Open AccessHsp70-Hsp110 chaperones deliver ubiquitin dependent and independent substrates to the 26S proteasome for proteolysis
Author(s) -
Ganapathi Kandasamy,
Claes Andréasson
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.210948
Subject(s) - proteasome , ubiquitin , biology , chaperone (clinical) , proteolysis , microbiology and biotechnology , hsp70 , protein degradation , ubiquitin protein ligases , biochemistry , ubiquitin ligase , heat shock protein , enzyme , medicine , pathology , gene
In protein quality control, proteotoxic misfolded proteins are recognized by molecular chaperones, ubiquitylated by dedicated quality-control ligases and delivered to 26S proteasome for degradation. The chaperone Hsp70 and its nucleotide exchange factor Hsp110 functions in the degradation of misfolded proteins by the ubiquitin-proteasome system via poorly understood mechanisms. Here we report that yeast Hsp110 (Sse1 and Sse2) functions in the degradation of Hsp70-associated ubiquitin conjugates at the post-ubiquitylation step and is required for the proteasomal degradation of ubiquitin-independent substrates. Hsp110 associates with the 19S regulatory particle of the 26S proteasome and interacts with Hsp70 to facilitate the delivery of Hsp70 substrates for proteasomal degradation. Using a highly defined ubiquitin-independent proteasome substrate we show that the mere introduction of a single Hsp70-binding site renders its degradation dependent on Hsp110. The findings define a dedicated and chaperone-dependent pathway for the efficient shuttling of cellular proteins to the proteasome with profound implications for understanding protein quality control and cellular stress management.