Localized Proteasomal Degradation: From the Nucleus to Cell Periphery

The proteasome is responsible for selective degradation of most cellular proteins. Abundantly present in the cell, proteasomes not only diffuse in the cytoplasm and the nucleus but also associate with the chromatin, cytoskeleton, various membranes and membraneless organelles/condensates. How and why the proteasome gets to these specific subcellular compartments remains poorly understood, although increasing evidence supports the hypothesis that intracellular localization may have profound impacts on the activity, substrate accessibility and stability/integrity of the proteasome. In this short review, I summarize recent advances on the functions, regulations and targeting mechanisms of proteasomes, especially those localized to the nuclear condensates and membrane structures of the cell, and I discuss the biological significance thereof in mediating compartmentalized protein degradation.