Hybrid Proteasomes

By N. Tanahashi, Y. Murakami, Y. Minami, N. Shimbara, K. Hendil, Keiji Tanaka. Journal of Biological Chemistry, 2000

323 citations recorded by the source corpus.

Eukaryotic cells contain various types of proteasomes. Core 20 S proteasomes (abbreviated 20 S below) have two binding sites for the regulatory particles, PA700 and PA28. PA700–20 S-PA700 complexes are known as 26 S proteasomes and are ATP-dependent machines that degrade cell proteins. PA28 is found both in previously described complexes of the type PA28–20 S-PA28 and in complexes that also contain PA700, as PA700–20 S-PA28. We refer to the latter as “hybrid proteasomes.” The relative amounts of the various types of proteasomes in HeLa extracts were determined by a combination of immunoprecipitation and immunoblotting. Hybrid proteasomes accounted for about a fourth of all proteasomes in the extracts. Association of PA28 and proteasomes proved to be ATP-dependent. Hybrid proteasomes catalyzed ATP-dependent degradation of ornithine decarboxylase (ODC) without ubiquitinylation, as do 26 S proteasomes. In contrast, the homo-PA28 complex (PA28–20 S-PA28) was incapable of degrading ODC. Intriguingly, a major immunomodulatory cytokine, interferon-γ, appreciably enhanced the ODC degradation in HeLa and SW620 cells through induction of the hybrid proteasome, which may also be responsible for the immunological processing of intracellular antigens. Taken together, we report here for the first time the existence of two types of ATP-dependent proteases, the 26 S proteasome and the hybrid proteasome, which appear to share the ATP-dependent proteolytic pathway in mammalian cells.

Subfields: Epidemiology, Molecular Biology, Parasitology

View Paper: https://www.semanticscholar.org/paper/2cefbbd868af6302d36b9b9e947c52314048eaec

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Immunoproteasome assembly and antigen presentation in mice lacking both PA28α and PA28β (2001, methodology): “These mice showed decreased ATP-dependent proteolytic activities, indicating that `hybrid proteasomes' that contain both PA28 and PA700 (Hendil et al., 1998; Tanahashi et al., 2000) are involved in protein degradation in the cells.”
T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-γ (2000, background): “, also activate the proteasome complex participating in the ATP-dependent proteolysi”
Proteasomes and their kin: proteases in the machine age (2004, background): “It is therefore probable that the PA28 regulator, which might associate to form a hybrid PA28–20S–19S particl”