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Opposing roles of U bp3‐dependent deubiquitination regulate replicative life span and heat resistance
Author(s) -
Öling David,
Eisele Frederik,
Kvint Kristian,
Nyström Thomas
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/embj.201386822
Subject(s) - biology , life span , heat resistance , microbiology and biotechnology , resistance (ecology) , genetics , evolutionary biology , ecology , materials science , composite material
The interplay between molecular chaperones, ubiquitin/deubiquitinating enzymes, and proteasomes is a critical element in protein homeostasis. Among these factors, the conserved deubiquitinase, Ubp3, has the interesting ability, when overproduced, to suppress the requirement for the major cytosolic Hsp70 chaperones. Here, we show that Ubp3 overproduction counteracts deficiency of Hsp70s by the removal of damaged proteins deposited in inclusion bodies ( JUNQ ) during both aging and heat stress. Consistent with this, Ubp3 destabilized, deubiquitinated, and diminished the toxicity of the JUNQ ‐associated misfolded protein Ubc9 ts in a proteasome‐dependent manner. In contrast, another misfolded model protein, ∆ss CPY *, was stabilized by Ubp3‐dependent deubiquitination demonstrating a dual role for Ubp3, saving or destroying aberrant protein species depending on the stage at which the damaged protein is committed for destruction. We present genetic evidence for the former of these activities being key to Ubp3‐dependent suppression of heat sensitivity in Hsp70‐deficient cells, whereas protein destruction suppresses accelerated aging. We discuss the data in view of how heat stress and aging might elicit differential damage and challenges on the protein homeostasis network.