RT Journal Article
T1 Limiting 20S proteasome assembly leads to unbalanced nucleo-cytoplasmic distribution of 26S/30S proteasomes and chronic proteotoxicity
A1 Ruiz Romero, Gabriel
A1 Berdún Reina, María Dolores
A1 Hochstrasser, Mark
A1 Salas-Pino, Silvia
A1 Rodríguez Daga, Rafael
K1 Proteasome
K1 Folding stress
K1 Yeast
AB 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.
PB Cell Press
YR 2024
FD 2024-11-24
LK https://hdl.handle.net/10433/25060
UL https://hdl.handle.net/10433/25060
LA en
NO iScience. 2024 Oct 4;27(11):111095
NO Artículo científico
NO Centro Andaluz de Biología del Desarrollo
NO Departamento de Biología Molecular e Ingeniería Bioquímica
DS RIO
RD Apr 25, 2026