The deubiquitylase USP9X controls ribosomal stalling.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
received:
27
04
2020
accepted:
11
12
2020
entrez:
28
1
2021
pubmed:
29
1
2021
medline:
10
9
2021
Statut:
ppublish
Résumé
When a ribosome stalls during translation, it runs the risk of collision with a trailing ribosome. Such an encounter leads to the formation of a stable di-ribosome complex, which needs to be resolved by a dedicated machinery. The initial stalling and the subsequent resolution of di-ribosomal complexes requires activity of Makorin and ZNF598 ubiquitin E3 ligases, respectively, through ubiquitylation of the eS10 and uS10 subunits of the ribosome. We have developed a specific small-molecule inhibitor of the deubiquitylase USP9X. Proteomics analysis, following inhibitor treatment of HCT116 cells, confirms previous reports linking USP9X with centrosome-associated protein stability but also reveals a loss of Makorin 2 and ZNF598. We show that USP9X interacts with both these ubiquitin E3 ligases, regulating their abundance through the control of protein stability. In the absence of USP9X or following chemical inhibition of its catalytic activity, levels of Makorins and ZNF598 are diminished, and the ribosomal quality control pathway is impaired.
Identifiants
pubmed: 33507233
pii: 211735
doi: 10.1083/jcb.202004211
pmc: PMC7849821
pii:
doi:
Substances chimiques
Antibodies
0
Carrier Proteins
0
MKRN2 protein, human
0
Ribonucleoproteins
0
USP9X protein, human
0
ZNF598 protein, human
0
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MR/N013840/1
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021 Clancy et al.
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