What is it about?

Proteasomes are large multisubunit complexes that are normally found diffusely spread in the nucleus and cytosol. However, under some conditions they come together and form cytosolic foci in yeast. In this work we tried to address what molecular interactions are responsible for keeping all these proteasomes tightly together in the cytosol. We found a critical role for the post-translational protein modification of long ubiquitin chains, several receptors that can binds these chains, namely those found on proteasomes themselves and on so called proteasome shuttle factors. We propose that these multivalent interactions drive the sorting of the proteasomes into these cytosolic foci.

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Why is it important?

Proteasomes play a critical role in the cell through their ability to degrade many proteins. Their regulation in the cell is therefore very important and relevant in diseases varying from cancer to neurodegenerative diseases. Besides being upregulated when there is increased need for its activity, proteasomes can also be redirected to form condensates (foci) in both yeast and human cells. The mechanism and physiological benefit of this relocalization, however, remain poorly understood. We identified interactions essential for this condensate formation. This will help us to understand what drives their formation and how these structures operate, thereby ultimately gaining understanding into their physiological function.


This project was started several years back and got slowed down when a lab member graduated. Two other lab members picked it up and all three first authors really worked together to tease out the interactions underlying the proteasome condensate formation. Very satisfying to provide insight the interactions that enable proteasomes to come together in the cytosol as well as to see the smooth collaboration between lab members that got us there.

Jeroen Roelofs
University of Kansas Medical Center

Read the Original

This page is a summary of: Proteasome condensate formation is driven by multivalent interactions with shuttle factors and ubiquitin chains, Proceedings of the National Academy of Sciences, February 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2310756121.
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