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.
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.
Inducing presomitic mesoderm (PSM)-fated ES cells clarified that Ripply2 directly interacts with Tbx6 and degrades Tbx6 in proteasome-ubiquitin pathway by recruiting the 26S proteasome, which is a PSM-specific event to define the segment border during mouse somitogenesis.
One α-synuclein strain inhibited proteasome activity and induced apparent pathologies, while the other did not, indicating a strain-dependent toxicity of α-synuclein aggregates, which support a prion-like behavior of α-synuclein.
The 26S proteasome lid subcomplex acts as an external scaffold whose interactions with the ATPase motor stabilize the substrate-engagement-competent state, and control conformational changes upon engagement for subsequent degradation steps.