Intracellular localization of proteasomes.

Proteasomes are present in the cytoplasm and in the nuclei of all eukaryotic cells, however their relative abundance within those compartments is highly variable. In the cytoplasm, proteasomes associate with the centrosomes, cytoskeletal networks and the outer surface of the endoplasmic reticulum (ER). In the nucleus, proteasomes are present throughout the nucleoplasm but are void from the nucleoli. Sometimes they associate with discrete subnuclear domains called the PML nuclear bodies (POD domains). PML bodies in the nucleus, and the pericentrosomal area of the cytoplasm may function as proteolytic centers of the cell, since they are enriched in components of the proteasome system. Under conditions of impaired proteolysis proteasomes and ubiquitinated proteins further accumulate at these locations, forming organized aggregates. In case of the pericentrosomal area those aggregates have been termed "aggresomes". Once formed, aggresomes can impair the function of the proteasome system, which may promote apoptosis. Under favorable conditions they can be cleared, probably by autophagy.