RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils

EMBO J. 2015 Sep 14;34(18):2363-82. doi: 10.15252/embj.201591245. Epub 2015 Aug 24.


The aggresome is an organelle that recruits aggregated proteins for storage and degradation. We performed an siRNA screen for proteins involved in aggresome formation and identified novel mammalian AAA+ protein disaggregases RuvbL1 and RuvbL2. Depletion of RuvbL1 or RuvbL2 suppressed aggresome formation and caused buildup of multiple cytoplasmic aggregates. Similarly, downregulation of RuvbL orthologs in yeast suppressed the formation of an aggresome-like body and enhanced the aggregate toxicity. In contrast, their overproduction enhanced the resistance to proteotoxic stress independently of chaperone Hsp104. Mammalian RuvbL associated with the aggresome, and the aggresome substrate synphilin-1 interacted directly with the RuvbL1 barrel-like structure near the opening of the central channel. Importantly, polypeptides with unfolded structures and amyloid fibrils stimulated the ATPase activity of RuvbL. Finally, disassembly of protein aggregates was promoted by RuvbL. These data indicate that RuvbL complexes serve as chaperones in protein disaggregation.

Keywords: RuvbL; aggresome; amyloid; disaggregation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Amyloid / genetics
  • Amyloid / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Organelles / genetics
  • Organelles / metabolism*
  • Organelles / pathology


  • Amyloid
  • Carrier Proteins
  • Heat-Shock Proteins
  • Nerve Tissue Proteins
  • SNCAIP protein, human
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • RUVBL1 protein, human
  • RUVBL2 protein, human