Min Jae Lee
Seoul National University, Korea
Title: Opening the core particle gate of mammalian proteasomes to enhance their degradatory activity
Biography
Biography: Min Jae Lee
Abstract
The proteasome core particle (CP) has the substrate translocation channel that is topologically blocked by the N-termini of the alpha subunits when it is in the closed form. For substrate degradation, the gate of CP channels is opened upon association with the regulatory particle (RP) or other proteasome activators. Here we show that deletion of the N-terminal tails of the alpha3 subunits (alpha3deltaN) constitutively opens the CP gate of mammalian proteasomes without affecting their structural integrity. The hyperactivity of open-gated alpha3deltaN proteasomes was observed both in 20S and 26S measured by small fluorogenic peptide substrates and polyubiquitinated Sic1 (Ub-Sic1). The cells, which express alpha3deltaN proteasomes showed significantly facilitated degradation of various proteasome substrates. Delayed aggregation formation of tau proteins, and promoted cell survival against oxidative stress. These data demonstrate that the regulation of CP gate function as a rate-limiting step of proteasomal degradation and opening the CP gate may be an effective strategy to increase proteasome activity and to reduce levels of aberrantly overexpressed proteins in cells.
