Hybrid Proteasomes

Abstract

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-␥, 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.

Proteasomal Inhibition by α-Synuclein Filaments and Oligomers

“…However, naked 20 S proteasomes account for about one-third of the 20 S proteasomal particles in mammalian cells (51), and hydrid proteasomes with 19 S particles attached to one end and the activator PA28 attached to the other end represent about 25% of 20 S proteasomes in HeLa cells (51). All proteasomal hydrolysis is carried out within the 20 S proteasome particle, and this can take two forms.…”

The role of the ubiquitin/proteasome system in cellular responses to radiation

“…Subcellular location of these structures may vary and critically determine function (Brooks et al, 2000). Hybrid proteasomes that contain one 19S and one 11S structure attached to the 20S core may play special roles (Tanahashi et al, 2000).…”

Inhibition of Proteasome Activity Induces Formation of Alternative Proteasome Complexes

“…Recruitment of proteasomal activators to the 20S catalytic core gives rise to a variety of different alternative proteasome complexes consisting of singly or doubly capped 20S proteasomes as well as hybrid complexes of different activators attached to 26S proteasomes (23,(27)(28)(29). Recent evidence indicates that the 20S and its activators may function as building blocks that assemble rapidly into different proteasome complexes with diverse functions and substrate specificities, allowing fast and dynamic adaptation of proteasome activity to cellular needs (30 -32).…”