Biological consequences of structural and functional proteasome diversity

Abstract

Cell homeostasis and regulation of metabolic pathways are ensured by synthesis, proper folding and efficient degradation of a vast amount of proteins. Ubiquitin-proteasome system (UPS) degrades most intracellular proteins and thus, participates in regulation of cellular metabolism. Within the UPS, proteasomes are the elements that perform substrate cleavage. However, the proteasomes in the organism are diverse. Structurally different proteasomes are present not only in different types of cells, but also in a single cell. The reason for proteasome heterogeneity is not fully understood. This review briefly encompasses mammalian proteasome structure and function, and discusses biological relevance of proteasome diversity for a range of important cellular functions including internal and external signaling.

The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 β

“…The β rings are composed of catalytically active subunits (β1, β2 and β5) that cleave peptide bonds at the C-terminal side of proteins [6] with caspase-, trypsin-and chymotrypsin-like activities, respectively [7,8]. The standard 26S proteasome contains a 19S regulatory cap that binds the polyubiquitin chain, denatures the protein, and feeds it into the proteolytic core of the proteasome [9].…”

The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, non-toxic concentrations of interleukin 1 β

“…Re-analysis of the previously published data set of single-cell RNA sequencing (37) uncovered substantial subpopulations of α-, β- and δ-cells that constitutively express all inducible subunits (Fig. 1A-B) placing human islets on par with other tissues that express those subunits constitutively (9, 16). When testing β cell models, as well as human and mouse islets, we found that all three inducible β-subunits were detectable at the protein level without the need for cytokine stimulation (Fig.…”

“…The β rings are composed of catalytically active subunits (β1, β2 and β5) that cleave peptide bonds at the C-terminal side of proteins (6) with caspase-, trypsin- and chymotrypsin-like activities, respectively (7, 8). The standard 26S proteasome contains a 19S regulatory cap that binds the polyubiquitin chain, denatures the protein, and feeds it into the proteolytic core of the proteasome (9).…”

“…Formation of the proteolytic core of these specialized proteasomes involves substitution of the constitutively expressed catalytic β1, β2 and β5 subunits with the interferon (IFN)-γ-inducible β1i, β2i and β5i subunits (alternatively termed Psmb9/LMP2, Psmb10/MECL-1/LMP10 and Psmb8/LMP7, respectively) (6, 10, 11). The immune-proteasome (i-proteasome) has an alternative 20S catalytic core where all β-subunits are replaced by IFN-γ inducible β-subunits and where the 20S-associated 19S can be replaced by the 11S (also termed PA28αβ) proteasome regulator (9, 12, 13).…”

“…Immune cells permanently and many other cells under conditions of oxidative stress, inflammation, cytokine stimulation, or viral and bacterial infection express and assemble i-and int-proteasomes (9, 19). Recently, induction of expression of such proteasomes upon exposure of human pancreatic islets and rat and mouse insulinoma cells to INFγ and β but not toxic concentrations of IL-1β, was reported (18, 20).…”