Interaction of U-box E3 ligase SNEV with PSMB4, the β7 subunit of the 20 S proteasome

Marlies Löscher, Klaus Fortschegger, Gustav Ritter, Martina Wostry, Regina Voglauer, Johannes A. Schmid, Steven Watters, A. Jennifer Rivett, Paul M. Ajuh, Angus I. Lamond, Hermann Katinger, Johannes Grillari

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Abstract

Recognition of specific substrates for degradation by the ubiquitin-proteasome pathway is ensured by a cascade of ubiquitin transferases E1, E2 and E3. The mechanism by which the target proteins are transported to the proteasome is not clear, but two yeast E3s and one mammalian E3 ligase seem to be involved in the delivery of targets to the proteasome, by escorting them and by binding to the 19 S regulatory particle of the proteasome. In the present study, we show that SNEV (senescence evasion factor), a protein with in vitro E3 ligase activity, which is also involved in DNA repair and splicing, associates with the proteasome by directly binding to the β7 subunit of the 20 S proteasome. Upon inhibition of proteasome activity, SNEV does not accumulate within the cells although its co-localization with the proteasome increases significantly. Since immunofluorescence microscopy also shows increased co-localization of SNEV with ubiquitin after proteasome inhibition, without SNEV being ubiquitinated by itself, we suggest that SNEV shows E3 ligase activity not only in vitro but also in vivo and escorts its substrate to the proteasome. Since the yeast homologue of SNEV, Prp19, also interacts with the yeast β7 subunit of the proteasome, this mechanism seems to be conserved during evolution. Therefore these results support the hypothesis that E3 ligases might generally be involved in substrate transport to the proteasome. Additionally, our results provide the first evidence for a physical link between components of the ubiquitin-proteasome system and the spliceosome.

Original languageEnglish
Pages (from-to)593-603
Number of pages11
JournalBiochemical Journal
Volume388
Issue number2
DOIs
Publication statusPublished - 1 Jun 2005

Keywords

  • 20 S proteasome
  • Pre4
  • Prp19
  • PSMb4
  • Senescence evasion factor (SNEV)
  • Spliceosome

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    Löscher, M., Fortschegger, K., Ritter, G., Wostry, M., Voglauer, R., Schmid, J. A., Watters, S., Rivett, A. J., Ajuh, P. M., Lamond, A. I., Katinger, H., & Grillari, J. (2005). Interaction of U-box E3 ligase SNEV with PSMB4, the β7 subunit of the 20 S proteasome. Biochemical Journal, 388(2), 593-603. https://doi.org/10.1042/BJ20041517