Exploring the proteasome system: A novel concept of proteasome inhibition and regulation

Abstract

Table 1 (Continued) HGNC ID (gene) Approved symbol Approved name Alternative protein names Synonyms HGNC:9564

Mitochondrial Regulation of the 26S Proteasome

“…Of note, reversible adjustment of 26S proteasome assembly was also evident in other cell types, i.e., MEFs and primary human skin or lung fibroblasts, indicating a robust and conserved mechanism of metabolic fine-tuning of proteasome function. These findings add an important aspect of proteasome regulation and fit to the emerging concepts of fine-tuning of proteasome activity and also ribosome function according to cellular needs (Emmott et al, 2019;Meiners et al, 2014;Rousseau and Bertolotti, 2018;Wang et al, 2020).…”

“…This finding was confirmed for RNA expression by RNA sequencing (Figure 1C; Table S1) and quantitative reverse transcriptase PCR (qRT-PCR) analysis for selected proteasome encoding genes (Figure S1E). For an overview on the divergent protein and gene names of proteasomal subunits, the reader is referred to Wang et al (2020). We next used native gels with substrate overlay analysis and immunoblotting to resolve the different active proteasome complexes in the cell.…”

In-gel proteasome assay to determine the activity, amount, and composition of proteasome complexes from mammalian cells or tissues

“…You can also determine the ratio between 26S and 20S proteasome complexes. Some of the singly capped 26S and 20S complexes might contain additional proteasome regulators ( Wang, Meul and Meiners, 2020 ) which can be detected by probing with specific antibodies against these regulators (see key resource table for more details). This will then provide you with more information about the composition of proteasome complexes in your sample as for examples shown by Welk et al., ( Welk et al., 2016 ).…”

At the Cutting Edge against Cancer: A Perspective on Immunoproteasome and Immune Checkpoints Modulation as a Potential Therapeutic Intervention

“…It is characterized by the presence of a specific α4 subunit (α4s) (PMSA8 gene) that replaces the constitutive α4: the incorporation of this subunit into a newly formed 20S is mutually exclusive with wild-type α4 and seems not to alter the constitutive catalytic specificity of the 20S [ 69 , 70 ]. Nevertheless, α4s incorporation seems to promote the association of the 20S with an alternative regulatory particle named PA200, a nuclear-specific proteasome activator expressed in all mammalian tissues, but particularly abundant in the testis, where it plays a crucial role in spermatogenesis [ 71 , 72 , 73 , 74 , 75 ]. Remarkably, an increase of PSMA8 expression has been reported in different tumors, such as large B cell lymphoma, thymomas, and testicular germ cell tumors, even though its pathophysiological meaning and relevance as a novel therapeutic target have not been investigated yet [ 69 , 76 , 77 ].…”