Hul5 HECT ubiquitin ligase plays a major role in the ubiquitylation and turnover of cytosolic misfolded proteins

The ubiquitin–proteasome system clears misfolded proteins to maintain cellular homeostasis. Mayor and colleagues identify the ubiquitin ligase Hul5 as a critical component of the heat-shock response and show that it selectively targets misfolded cytosolic proteins for degradation.