Clancy, Anne, Heride, Claire, Pinto-Fernandez, Adan, Elcocks, Hannah, Kallinos, Andreas ORCID: 0000-0001-8771-963X, Kayser-Bricker, Katherine J, Wang, Weiping, Smith, Victoria, Davis, Simon, Fessler, Shawn et al (show 16 more authors)
(2021)
The deubiquitylase USP9X controls ribosomal stalling.
JOURNAL OF CELL BIOLOGY, 220 (3).
e202004211-.
Abstract
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.
Item Type: | Article |
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Uncontrolled Keywords: | Cell Line, Tumor, Ribosomes, Humans, Ubiquitin Thiolesterase, Carrier Proteins, Ribonucleoproteins, Antibodies, Reproducibility of Results, Ubiquitination, Biocatalysis, Protein Stability, HEK293 Cells |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
Depositing User: | Symplectic Admin |
Date Deposited: | 08 Jul 2021 08:59 |
Last Modified: | 18 Jan 2023 21:36 |
DOI: | 10.1083/jcb.202004211 |
Open Access URL: | https://doi.org/10.1083/jcb.202004211 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3129259 |