Experimental and computational analyses reveal how proteasomal hydrolysis is regulated and show that peptide transport is the rate-limiting step and the main differentiating factor between human standard- and immuno-proteasomes.
Within the isolated lid sub-complex of the proteasome, a finely tuned network of interactions maintains the deubiquitinase in an inhibited conformation; dramatic rearrangements of the lid subunits upon incorporation into the holoenzyme lead to the deubiquitinase’s activation.
Structures of active and inactive conformations of a PP2C family phosphatase reveal a conserved switch that controls enzymatic activity and point to an unexpected relationship between phosphatases and proteasomal proteases.
Faithful models of RMC require SMARCB1 loss for survival, and genetic and small-molecule screens identify inhibition of the ubiquitin-proteasome system (UPS) as a potential therapeutic approach for SMARCB1 deficient cancers.
Proteasomes are protected from autophagic elimination upon carbon starvation by sequestration into cytoplasmic storage granules, which aid cell fitness by providing a cache of proteasomes that can be rapidly remobilized when carbon availability improves.