Disease relevance of 20S

• A mouse fibroblast line expressing the murine cytomegalovirus pp89 protein was transfected with either the human or murine gene encoding the PA28alpha subunit, which is sufficient to activate the peptide-hydrolysing activity of the 20S proteasome in vitro [1].
• Early region 2 of the adenovirus 2 genome (map position 61-75) specifies two poly(A)+ nuclear RNAs (28S and 23S) that appear to be precursors of the 20S cytoplasmic mRNA [Goldenberg, C. J. & Raskas, H. J. (1979) Cell 16, 131-138] [2].
• Elevated levels of total ubiquitinated proteins and 19S and 20S proteasome subunits are evident in both low-grade and high-grade ovarian carcinoma tissues relative to benign ovarian tumors and in ovarian carcinoma cell lines relative to immortalized surface epithelium [3].
• Here, we report, for the first time, that Celastrol potently and preferentially inhibits the chymotrypsin-like activity of a purified 20S proteasome (IC(50) = 2.5 micromol/L) and human prostate cancer cellular 26S proteasome (at 1-5 micromol/L) [4].
• Digestion of the extended vesicular stomatitis virus nucleoprotein epitope 52-59 (RGYVYQGL) by the 20S proteasome in vitro shows that the proteasome is capable of generating the correct C terminus but not the exact N terminus of the CTL epitope [5].

High impact information on 20S

• We analyzed the kinetics of product generation by 20S proteasomes with and without PA28 [6].
• This labels the proteins for rapid hydrolysis to oligopeptides by a (26S) proteolytic complex containing a (20S) degradative particle called the proteasome [7].
• In addition, purified 26S proteasome complex, but not the 20S proteasome, catalyses ODC degradation in the absence of ubiquitin [8].
• Subunit of the '20S' proteasome (multicatalytic proteinase) encoded by the major histocompatibility complex [9].
• Tritium-labeled lactacystin was used to identify the 20S proteasome as its specific cellular target [10].

Biological context of 20S

• We propose tissue-specific antigen processing by 20S proteasomes as a potential mechanism to control organ-specific immune responses [11].
• IFN-gamma stimulation results in a downregulation of the chymotrypsin-like Suc-LLVY-MCA peptide hydrolyzing activity of 20S proteasomes whereas the trypsin-like activity remains unaffected [12].
• Structurally different inhibitors that bind to specific catalytic beta subunits of the 20S proteasome stimulated bone formation in bone organ cultures in concentrations as low as 10 nM [13].
• Here we describe a novel requirement in thymocyte cell death for the 20S proteasome, a highly conserved multicatalytic protease found in all eukaryotes [14].
• Proteasomal 20S core catalytic component was redistributed to the polyglutamine aggregates in both the cellular and transgenic mouse models [15].

Anatomical context of 20S

• At least 36 distinct subunits (17 of 20S and 19 of 19S) are coexpressed and assembled as 26S proteasomes in this vital cardiac organelle, whereas the expression of PA200 and 11S subunits were detected with limited participation in the 26S complexes [16].
• Digests of HSP60 polypeptides by 20S proteasomes show most efficient generation of the pathology related CD8(+) T cell epitope in the small intestine [11].
• A hallmark of these so-called polyglutamine diseases is the presence of ubiquitylated inclusion bodies, which sequester various components of the 19S and 20S proteasomes [17].
• Interference with both T cell growth and effector function was mediated by blockade of the catalytic activities of the 20S/26S proteasome complex, resulting in intracellular accumulation of IkappaB-alpha and subsequent inhibition of NF-kappaB activation [18].
• The subunit protein composition of 20S proteasomes purified from liver, thymus, and lung reflected RNA expression [19].

Associations of 20S with chemical compounds

• The papain superfamily member bleomycin hydrolase (Blmh) is a neutral cysteine protease with structural similarity to a 20S proteasome [20].
• Total cellular polyadenylated Py-specific RNA molecules having an S value in the range of 16S to 20S were purified by oligodeoxythymidylic acidcellulose column chromatography, preparative hybridization with Py DNA, and sucrose gradient centrifugation [21].
• Our data show that tetracycline-regulated expression of PA28 increases CTL epitope generation without affecting the 20S proteasome composition or half-life [22].
• A potential molecular target was found: ritonavir selectively inhibited the chymotrypsin-like activity of the 20S proteasome [23].
• After depletion of Mpp10p by growth in glucose, cell growth is arrested and levels of 18S and its 20S precursor are reduced or absent while the 23S and 35S precursors accumulate [24].

Physical interactions of 20S

• The proteasome inhibitor PI31 competes with PA28 for binding to 20S proteasomes [25].
• The mouse Lmp-2 gene is located within the major histocompatibility complex (MHC) class II region and encodes a subunit of the 20S cytosolic proteasome [26].
• PA28alpha/beta is a regulatory complex of the 20S proteasome which consists of two IFN-gamma inducible subunits [27].
• The 20S proteasome is the enzyme complex responsible for the processing of antigens bound by major histocompatibility complex class I molecules [28].

Regulatory relationships of 20S

• The proteasome regulator PA28alpha/beta can enhance antigen presentation without affecting 20S proteasome subunit composition [27].
• Inactivation of a defined active site in the mouse 20S proteasome complex enhances major histocompatibility complex class I antigen presentation of a murine cytomegalovirus protein [29].
• A third interferon-gamma-induced subunit exchange in the 20S proteasome [30].
• 15(S)-HETE induced phosphorylation and degradation of IkappaBalpha at the same concentrations as those inducing 20S proteasome expression, and this effect was attenuated by calphostin C, suggesting the mediation of PKC [31].

Other interactions of 20S

• AIRAP's association with the 19S cap reverses the stabilizing affect of ATP on the 26S proteasome during particle purification, and AIRAP-containing proteasomes, though constituted of 19S and 20S subunits, acquire features of hybrid proteasomes with both 19S and 11S regulatory caps [32].
• 5080 T did not oligomerize beyond 5 to 10S in size compared with normal T, which oligomerized predominantly to 14 to 20S species [33].
• This process of NQO1-regulated ODC degradation was recapitulated in vitro by using purified 20S proteasomes [34].
• Two members of the proteasome activator, PA28alpha and PA28beta, form a heteropolymer that binds to both ends of the 20S proteasome [35].
• These genetic data rigorously demonstrate control of the P3-450 (20S) mRNA induction process by the Ah receptor. pP(3)450-21 fragments hybridized to TCDD-induced C57BL/6N mRNA and to a portion of the cloned 5' end of the P1-450 gene from a mouse MOPC 41 plasmacytoma library.(ABSTRACT TRUNCATED AT 250 WORDS)[36]

Analytical, diagnostic and therapeutic context of 20S

• Electron microscopy of the resulting structures revealed one PA28 ring at one end of the 20S particle and a 19S complex at the other [37].
• SDS-PAGE analysis of the photoaffinity-labeled proteasome showed that low molecular weight bands (approximately 21-31 kDa) of 20S proteasome had the highest photoaffinity [38].
• Samples of intact OVA and beta-galactosidase were subjected to digestion in vitro by 20S proteasome purified from bovine red cells and the resulting peptide mixtures were fractionated by reverse-phase HPLC [39].
• Atomic force microscopy (AFM) studies demonstrate that 20S and 26S proteasomes treated with PR39 or its derivatives exhibit serious perturbations in their structure and their normal allosteric movements [40].
• There was also increased protein levels of the 20S proteasome core and 19S regulatory subunit, detectable by immunoblotting, suggesting activation of the ATP-ubiquitin-dependent proteolytic pathway [41].

References