The deubiquitylase USP9X controls ribosomal stalling

• DOI: 10.1083/jcb.202004211
• Publication Date: 2021-01-28T21:45:02Z
• Authors: Anne Clancy; Claire Heride; Adán Pinto-Fernández; Hannah Elcocks; Andreas Kallinos; Katherine J. Kays...; 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
• Keywords: Ribosomal protein

When a ribosome stalls during translation, it runs the risk of collision with trailing ribosome. Such an encounter leads to formation stable di-ribosome complex, which needs be resolved by dedicated machinery. The initial stalling and subsequent resolution di-ribosomal complexes requires activity Makorin ZNF598 ubiquitin E3 ligases, respectively, through ubiquitylation eS10 uS10 subunits We have developed specific small-molecule inhibitor deubiquitylase USP9X. Proteomics analysis, following treatment HCT116 cells, confirms previous reports linking USP9X centrosome-associated protein stability but also reveals loss 2 ZNF598. show that interacts both these regulating their abundance control stability. In absence or chemical inhibition its catalytic activity, levels Makorins are diminished, ribosomal quality pathway is impaired.