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Identity of the 19S 'prosome' particle with the large multifunctional protease complex of mammalian cells (the proteasome)

Abstract

There have been many reports that eukaryotic cells contain ring-shaped 19S or 20S particles which are composed of numerous polypeptide subunits ranging in size between 25 and 35 kilodaltons1–12. Because these particles seemed to copurify with inactive mRNA, they were assumed to function in regulating mRNA translation8,12 and hence were named 'prosomes' (for 'program-med-o-some')8. A number of properties have been reported for these structures, including an association with specific RNA species3'8–12 or with certain heat-shock proteins10 and involvement in tRNA processing13 or aminoacyl tRNA synthesis1. However, these proposed activities have not been supported by definitive evidence. During studies of the proteolytic systems in mammalian tissues14–17, we noted many similarities between these 19S particles and the high molecular weight protease complexes that are present in most or all eukaryotic cells14–24. This (700 kilodalton) enzyme complex, designated here as LAMP for 'large alkaline multifunctional protease', contains three distinct endoproteolytic sites which function at neutral or alkaline pH and are specific for hydrolysis of proteins, hydrophobic peptides, or basic peptides14–19. This protease also exists in a latent form which can be activated by polylysine14'16, fatty acids19, or ATP17,25–28. In this report, we show that the prosomes and these protease complexes are very similar or identical with respect to their size, polypeptide composition, immunological cross-reactivity, appearance in the electron microscope, radial symmetry of subunits, subcellular localization, and proteolytic activities. Therefore, the 'prosome' probably plays a critical role in intracellular protein breakdown, and we propose that it be renamed 'proteasome'.

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Arrigo, AP., Tanaka, K., Goldberg, A. et al. Identity of the 19S 'prosome' particle with the large multifunctional protease complex of mammalian cells (the proteasome). Nature 331, 192–194 (1988). https://doi.org/10.1038/331192a0

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