An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity.

Sigalit Sukenik, Ilana Braunstein, Ariel Stanhill

Biomolecules 2021 Sep 06

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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.

Citation

Sigalit Sukenik, Ilana Braunstein, Ariel Stanhill. An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity. Biomolecules. 2021 Sep 06;11(9)