%0 Journal Article
%A Ruiz Romero, Gabriel
%A Berdún Reina, María Dolores
%A Hochstrasser, Mark
%A Salas-Pino, Silvia
%A Rodríguez Daga, Rafael
%T Limiting 20S proteasome assembly leads to unbalanced nucleo-cytoplasmic distribution of 26S/30S proteasomes and chronic proteotoxicity
%D 2024
%U https://hdl.handle.net/10433/25060
%X In addition to the degradation of cell-cycle proteins, short-lived, damaged, or unfolded proteins areconstantly cleared from cells by the proteasome. During proliferation, the proteasome localizes to the nucleus and cytoplasm; however, the functional relevance of this compartmentalization remains unclear.Here, we show that folding stress increases 26S/30S proteasome activity, which correlates with the upregulation of Ump1, a chaperone involved in 20S assembly. Conversely, ump1 inactivation results in a dropof 20S and 26S/30S proteasomes. Limited 26S/30S proteasomes in ump1-deficient cells accumulate in thenucleus where they degrade mitotic substrates, allowing cells to proceed through mitosis; however, thesecells present cytoplasmic aggregates and constitutive activation of the heat shock response. Thus, ourdata suggest that an increase in proteasome assembly induced by folding stress functions as an additionallayer to proteasome regulation and highlight the importance of balanced proteasome compartmentalization to sustain cell proliferation while maintaining proper cytoplasmic proteostasis.
%K Proteasome
%K Folding stress
%K Yeast
%~