The Contribution of the 20S Proteasome to Proteostasis

Abstract

The last decade has seen accumulating evidence of various proteins being degraded by the core 20S proteasome, without its regulatory particle(s). Here, we will describe recent advances in our knowledge of the functional aspects of the 20S proteasome, exploring several different systems and processes. These include neuronal communication, post-translational processing, oxidative stress, intrinsically disordered protein regulation, and extracellular proteasomes. Taken together, these findings suggest that the 20S proteasome, like the well-studied 26S proteasome, is involved in multiple biological processes. Clarifying our understanding of its workings calls for a transformation in our perception of 20S proteasome-mediated degradation—no longer as a passive and marginal path, but rather as an independent, coordinated biological process. Nevertheless, in spite of impressive progress made thus far, the field still lags far behind the front lines of 26S proteasome research. Therefore, we also touch on the gaps in our knowledge of the 20S proteasome that remain to be bridged in the future.

Mild proteasomal stress improves photosynthetic performance in Arabidopsis chloroplasts

“…We obtained the following mutant lines from the NASC collection, i.e., SALK_151595C (rpn8a), SALK_128568C (rpn8b), SALK_047984C (pad1) in the Col-background (wildtype reference). The sp1 (SALK_063571) and ppi2 mutants (Toc159, CS11072 introgressed into the Columbia-0 ecotype) are as previously reported 9,32 . Double mutants rpn8a ppi2, sp1 ppi2, rpn8b ppi2, and pad1 ppi2 were crossed with the above referenced genotypes using heterozygous ppi2 plants.…”

“…Thus, a general reduction of proteasomal activity has an effect on chloroplast protein abundance that is different from the rpn8a mutation. This is not surprising because the 20S proteasome removes damaged proteins under conditions of oxidative stress 9 and inhibition of its activity by MG132 interferes with this important function 25 .…”

“…6a-c). This is plausible because the transitpeptide creates a disordered region that makes precursors an efficient natural target for 20S proteasomal degradation 9 . However, our data show that this is not the mechanism responsible for the phenotype observed here.…”

“…The RP consists of a lid that is responsible for substrate recognition and binding and a base that transfers proteins to the catalytic core. CP and RP may exist and function independently of each other, as exemplified by the upregulation of the CP under conditions of oxidative stress 8,9 .…”

Signature activities of 20S proteasome include degradation of the ubiquitin-tag with the protein under hypoxia

“…Although the 20S subcomplex is an integral part of the 26S holoenzyme, it is quite abundant as a free complex in many cell types (Fabre et al, 2014). It has been suggested that free 20S may be a proteasome assembly intermediate, a 26S breakdown product (due to disassembly), or a stand-alone proteolytic enzyme (Bajorek et al, 2003;Demasi and da Cunha, 2018;Hendil et al, 2009;Hohn and Grune, 2014;Jung and Grune, 2008;Kumar Deshmukh et al, 2019;Livnat-Levanon et al, 2014l;Njomen et al, 2018;Pickering and Davies, 2012;Raynes et al, 2016;Sahara et al, 2014;Tomko and Hochstrasser, 2013;Tsvetkov et al, 2015). For instance, prokaryotes, which lack ubiquitin, do have 20S complexes and other ATP-dependent proteases, supporting the notion of 20S being the primordial protein-degrading machine (Majumder and Baumeister, 2019).…”