Kuhn, K. D.; Cho, U. H.; Hetzer, M.

The acquisition of cellular identity requires large-scale alterations in cellular state. The non-canonical proteasome activator PSME3 is known to regulate diverse cellular processes, but its importance for differentiation remains unclear. Here, we demonstrate that PSME3 binds dynamically to highly active promoters over the course of differentiation. However, loss of PSME3 does not globally affect mRNA transcription. We find instead that PSME3 interacts with the HSP90 co-chaperone NUDC and regulates the levels of several cell adhesion-related proteins, such that loss of PSME3 results in increased cell motility. Further, we show that PSME3 facilitates myoblast differentiation in a proteasome-independent manner. Our findings reveal several new facets of PSME3 functionality and highlight its particular importance for the differentiation of myogenic cells.