Proteasomes are eukaryotic ring-shaped or cylindrical particles with multicatalytic protease activities. To clarify the involvement of proteasomes in tumorigenesis of human blood cells, we compared their expression in human hematopoietic malignant tumor cells with that in normal peripheral blood mononuclear cells. Immunohistochemical staining showed considerably increased concentrations of proteasomes in leukemic cells from the bone marrow of patients with various types of leukemia and the predominant localization of these proteasomes in the nuclei. Moreover, enzyme immunoassay and Northern blot analysis indicated that the concentrations of proteasomes and their mRNA levels were consistently much higher in a variety of malignant human hematopoietic cell lines than in resting peripheral lymphocytes and monocytes from healthy adults. Proteasome expression was also greatly increased in normal blood mononuclear cells during blastogenic transformation induced by phytohemagglutinin; their expression increased in parallel with induction of DNA synthesis and returned to the basal level with progress of the cell cycle. Thus, abnormally high expression of proteasomes may play an important role in transformation and proliferation of blood cells and in specific functions of hematopoietic tumor cells.named C2 (12) and C3 (13), from rat liver proteasomes and one component of 35 kDa of Drosophila proteasomes (14) have been determined by cDNA cloning. The overall amino acid sequence of rat C2 closely resembles that of the Drosophila 35-kDa protein, suggesting that these two components function similarly in most eukaryotes and that they evolved from the same ancestral gene. In contrast, no significant homologies of these components with any other known proteins were found by computer analysis, indicating that proteasomes are a novel type of enzyme complex.Proteasomes are ubiquitous in cells of eukaryotes ranging from humans to yeast (1,15,16). Moreover, proteasomes or the related 20S particles have been found in both the cytoplasm and the nuclei of a variety of mammalian cells (8,17,18) and also various lower eukaryotes (14,(19)(20)(21)(22)(23)(24)(25), suggesting that their diverse roles depend on their differential localizations in the cells. However, the exact function of proteasomes is still unknown. One way to obtain information on their physiological role(s) is to study their expression in cells in abnormal states. In this work, we examined the expression of proteasomes in resting and growth-stimulated normal peripheral blood mononuclear cells and in a variety of human hematopoietic tumor cell lines.Proteasomes are multicatalytic proteinase complexes that are thought to be major intracellular proteolytic enzyme complexes responsible for certain types of nonlysosomal pathways of protein breakdown that requires metabolic energy (1). They were found to catalyze the degradation of various proteins in an ATP-dependent fashion (2-4). Moreover, 20S proteasomes were demonstrated to assemble into 26S proteolytic complexes t...
Proteasomes (multicatalytic proteinase complexes), which are identical to the ubiquitous eukaryotic 20S particles, are localized in both the cytoplasm and the nucleus, but the mechanism of their co‐localization in the two compartments is unknown. On examination of the primary structures of subunits of proteasomes, a consensus sequence for nuclear translocation of proteins, X‐X‐K‐K(R)‐X‐K(R) (where X is any residue), was found to be present in some subunits and to be highly conserved in the subunits of a wide range of eukaryotes. In addition, proteasomal subunits were found to bear a cluster of acidic amino acid residues and also a potential tyrosine phosphorylation site that was located in the same polypeptide chain as the nuclear location signal. These structural properties suggest that two sets of clusters with positive and negative charges serve to regulate the translocation of proteasomes from the cytoplasm to the nucleus, and that phosphorylation of tyrosine in certain subunits may play an additional role in transfer of proteasomes into the nucleus.
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