G3BP1 inhibits ubiquitinated protein aggregations induced by p62 and USP10

Sci Rep. 2019 Sep 9;9(1):12896. doi: 10.1038/s41598-019-46237-1.


The aberrant accumulation of ubiquitinated protein aggregates in cells plays a critical role in the pathogenesis of several degenerative diseases, including Parkinson disease (PD) and cystic fibrosis (CF). In this study, we found that Ras GTPase-activating protein-binding protein 1 (G3BP1) inhibits ubiquitinated protein aggregations induced by p62 and USP10 in cultured cells. p62 is a ubiquitin receptor, and p62 and its binding partner USP10 have been shown to augment ubiquitinated protein aggregation. G3BP1 interacted with p62 and USP10 and inhibited p62/USP10-induced protein aggregation. The G3BP1 inhibition of protein aggregations targeted two aggregation-prone proteins, α-synuclein and CFTR-ΔF508, which are causative factors of PD and CF, respectively. G3BP1 depletion increased the amounts of ubiquitinated α-synuclein and CFTR-ΔF508 protein. A proteasome reporter indicated that G3BP1 depletion inhibits the proteasome activity. We herein present evidence that G3BP1, p62 and USP10 together control ubiquitinated protein toxicity by controlling both ubiquitination and aggregation. Taken together, these results suggest that G3BP1, p62 and USP10 could be therapeutic targets for ubiquitinated protein aggregation disorders, including PD and CF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DNA Helicases / deficiency*
  • DNA Helicases / genetics*
  • Gene Knockout Techniques*
  • Humans
  • Poly-ADP-Ribose Binding Proteins / deficiency*
  • Poly-ADP-Ribose Binding Proteins / genetics*
  • Proteasome Endopeptidase Complex / metabolism
  • RNA Helicases / deficiency*
  • RNA Helicases / genetics*
  • RNA Recognition Motif Proteins / deficiency*
  • RNA Recognition Motif Proteins / genetics*
  • RNA-Binding Proteins / metabolism*
  • Ubiquitin Thiolesterase / metabolism*
  • Ubiquitination*
  • alpha-Synuclein / metabolism


  • P62 protein, human
  • Poly-ADP-Ribose Binding Proteins
  • RNA Recognition Motif Proteins
  • RNA-Binding Proteins
  • USP10 protein, human
  • alpha-Synuclein
  • Ubiquitin Thiolesterase
  • Proteasome Endopeptidase Complex
  • DNA Helicases
  • G3BP1 protein, human
  • RNA Helicases