Kuhn Kenneth D, Cho Ukrae H, Hetzer Martin W
Institute of Science and Technology (ISTA), Klosterneuburg, Austria.
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Life Sci Alliance. 2025 Jun 19;8(9). doi: 10.26508/lsa.202503208. Print 2025 Sep.
The acquisition of cellular identity requires large-scale alterations in cellular state. The noncanonical 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 influences the levels of several adhesion-related proteins and acts upstream of the HSP90 co-chaperone NUDC to regulate cell motility and myoblast differentiation in a proteasome-independent manner. Our findings reveal several new facets of PSME3 functionality and highlight its importance for the differentiation of myogenic cells.
细胞身份的获得需要细胞状态的大规模改变。已知非经典蛋白酶体激活剂PSME3可调节多种细胞过程，但其对分化的重要性仍不清楚。在这里，我们证明PSME3在分化过程中动态结合到高活性启动子上。然而，PSME3的缺失并不会全局影响mRNA转录。相反，我们发现PSME3影响几种黏附相关蛋白的水平，并在HSP90共伴侣蛋白NUDC的上游发挥作用，以蛋白酶体非依赖的方式调节细胞运动和成肌细胞分化。我们的研究结果揭示了PSME3功能的几个新方面，并突出了其对成肌细胞分化的重要性。
