Proteasome articles from across Nature Portfolio

The proteasome core particle (CP) assembles through the fusion of two half-CP precursors, yielding a complete but immature CP structure. Here the authors identify by cryogenic electron microscopy the structure of a post-fusion assembly intermediate, revealing how associated factors collaborate to chaperone CP assembly and maturation.

mTOR inhibition by deprivation of the amino acids Tyr, Trp and Phe promotes the translocation of the 26S proteasome from the nucleus to the cytosol, which is required for stress tolerance and cell survival.

Cold temperature prolongs lifespan in nematodes by inducing ubiquitin-independent proteasome activity, which prevents protein aggregation and neuronal degeneration. The pathway is conserved in humans.

Moderately cold temperatures trigger the removal of aggregation-prone proteins in the invertebrate model Caenorhabditis elegans and cultured human cells, preventing the accumulation of pathological aggregates linked with age-related neurodegenerative disorders such as amyotrophic lateral sclerosis and Huntington’s disease.

Myocardial ischemia–reperfusion injury (MIRI) substantially contributes to the morbidity associated with ischemic heart disease. Timed administration of digoxin decreased the susceptibility of mouse cardiomyocytes to MIRI; digoxin acted by promoting proteasomal degradation of the nuclear receptor REV-ERBα, a key component of the molecular circadian clock.