An arsenite relay between psmd14 and airap enables revival of proteasomal dub activity

Sigalit Sukenik, Ilana Braunstein, Ariel Stanhill

Research output: Contribution to journalArticlepeer-review


Maintaining 26S proteasome activity under diverse physiological conditions is a fundamental requirement in order to maintain cellular proteostasis. Several quantitative and qualitative mechanisms have evolved to ensure that ubiquitin–proteasome system (UPS) substrates do not accumulate and lead to promiscuous protein–protein interactions that, in turn, lead to cellular malfunction. In this report, we demonstrate that Arsenite Inducible Regulatory Particle-Associate Protein (AIRAP), previously reported as a proteasomal adaptor required for maintaining proteasomal flux during arsenite exposure, can directly bind arsenite molecules. We further show that arsenite inhibits Psmd14/Rpn11 metalloprotease deubiquitination activity by substituting zinc binding to the MPN/JAMM domain. The proteasomal adaptor AIRAP is able to directly relieve PSMD14/Rpn11 inhibition. A possible metal relay between arsenylated PSMD14/Rpn11 and AIRAP may serve as a cellular mechanism that senses proteasomal inhibition to restore Psmd14/Rpn11 activity.

Original languageEnglish
Article number1317
Issue number9
StatePublished - Sep 2021

Bibliographical note

Funding Information:
Funding: This research was funded by the Israeli Science Foundation (grant 497/08) and the Open University of Israel research fund (grant 41135).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Arsenite
  • PSMD14/RPN11
  • Proteasome
  • Protein misfolding
  • Proteostasis


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