| RRC ID |
54477
|
| Author |
Takahashi M, Kitaura H, Kakita A, Kakihana T, Katsuragi Y, Nameta M, Zhang L, Iwakura Y, Nawa H, Higuchi M, Komatsu M, Fujii M.
|
| Title |
USP10 Is a Driver of Ubiquitinated Protein Aggregation and Aggresome Formation to Inhibit Apoptosis.
|
| Journal |
iScience
|
| Abstract |
Accumulation of ubiquitinated proteins is cytotoxic, but cells inactivate these cytotoxicities by inducing aggresome formation. We found that ubiquitin-specific protease 10 (USP10) inhibits ubiquitinated protein-induced apoptosis by inducing aggresome formation. USP10 interacted with the ubiquitin receptor p62 and the interaction augmented p62-dependent ubiquitinated protein aggregation and aggresome formation, thereby cooperatively inhibiting apoptosis. We provide evidence that USP10/p62-induced protein aggregates inhibit proteasome activity, which increases the amount of ubiquitinated proteins and promotes aggresome formation. USP10 induced aggresomes containing α-synuclein, a pathogenic protein in Parkinson disease, in cultured cells. In Parkinson disease brains, USP10 was colocalized with α-synuclein in the disease-linked aggresome-like inclusion Lewy bodies, suggesting that USP10 inhibits α-synuclein-induced neurotoxicity by promoting Lewy body formation. Collectively, these findings suggest that USP10 is a critical factor to control protein aggregation, aggresome formation, and cytotoxicity in protein-aggregation-related diseases.
|
| Volume |
9
|
| Pages |
433-450
|
| Published |
2018-11-30
|
| DOI |
10.1016/j.isci.2018.11.006
|
| PII |
S2589-0042(18)30196-2
|
| PMID |
30469013
|
| PMC |
PMC6249355
|
| IF |
4.447
|
| Times Cited |
3
|
| Resource |
| DNA material |
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (RDB04393) |
