Akt can regulate the ubiquitin-proteasome system by mediating phosphorylation and activation of USP14, which may have implications in the control of global proteostasis by growth factors and in tumorigenesis.
Chemical perturbation-dependent deep mutational scanning data collected by a lab-based interdisciplinary graduate class resolves a paradox between the high evolution conservation and the high mutational tolerance of the protein ubiquitin.
In fruit flies, maternally deposited RNA-binding proteins are removed during the maternal-to-zygotic transition via a mechanism of translational upregulation of Kondo, the key E2 enzyme, at egg activation.
Temperature-sensitive mitochondrial outer membrane proteins used as novel quality control substrates reveal a unique mitochondria-associated degradation pathway consisting of both cytosolic and mitochondrial ubiquitin-proteasome system machinery.
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.
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.