The deubiquitylase USP9X controls ribosomal stalling.
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Date
2021-03-01ICR Author
Author
Clancy, A
Heride, C
Pinto-Fernández, A
Elcocks, H
Kallinos, A
Kayser-Bricker, KJ
Wang, W
Smith, V
Davis, S
Fessler, S
McKinnon, C
Katz, M
Hammonds, T
Jones, NP
O'Connell, J
Follows, B
Mischke, S
Caravella, JA
Ioannidis, S
Dinsmore, C
Kim, S
Behrens, A
Komander, D
Kessler, BM
Urbé, S
Clague, MJ
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Language
eng
Date accepted
2020-12-11
Citation
The Journal of cell biology, 2021, 220 (3)
Publisher
ROCKEFELLER UNIV PRESS