The deubiquitylase USP9X controls ribosomal stallingMore about Open Access at the Crick
Authors listAnne Clancy Claire Heride Adán Pinto-Fernández Hannah Elcocks Andreas Kallinos Katherine J Kayser-Bricker Weiping Wang Victoria Smith Simon Davis Shawn Fessler Crystal McKinnon Marie Katz Tim Hammonds Neil P Jones Jonathan O'Connell Bruce Follows Steven Mischke Justin A Caravella Stephanos Ioannidis Christopher Dinsmore Sunkyu Kim Axel Behrens David Komander Benedikt M Kessler Sylvie Urbé Michael J Clague
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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.
Journal The Journal of Cell Biology
Issue number 3