<i>PRE3</i>, highly homologous to the human major histocompatibility complex‐linked <i>LMP2 (RING12)</i> gene, codes for a yeast proteasome subunit necessary for the peptidylglutamyl‐peptide hydrolyzing activity

Enenkel, Cordula; Lehmann, H.; Kipper, Julia; Gückel, Roland; Hilt, Wolfgang; Wolf, Dieter H.

doi:10.1016/0014-5793(94)80455-9

Cited by 80 publications

(50 citation statements)

References 37 publications

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“…Yeast mutants deficient in proteasomal PGPH activity are mutated in the genes PRE3 and PRE4, the yeast homologues of delta and N3, respectively (12,13,38). Delta has the structural features of enzymatically active subunits while N3 does not (7).…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, 7 different types of ␤ subunits have been detected in yeast cells and 10 in various mammalian cells (9). Analysis of yeast mutants defective in the chymotryptic or peptidylglutamyl peptide hydrolyzing (PGPH) activities of the proteasome has shown that in these cases mutations in two different ␤ subunits were responsible for a single type of activity (10)(11)(12)(13). Apparently, cooperation between two different ␤ subunits is necessary for expression of a single activity and location of these subunits within the proteasome complex cannot be fortuitous.…”

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confidence: 99%

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Subunit arrangement in the human 20S proteasome

Köpp

Hendil

Dahlmann

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

110

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In human 20S proteasomes two copies of each of seven different ␣-type and seven different ␤-type subunits are assembled to form a stack of four sevenmembered rings, giving the general structure ␣ 1-7 , ␤ 1-7 , ␤ 1-7 , ␣ 1-7 . By means of immunoelectron microscopy and chemical crosslinking of neighboring subunits, we have determined the positions of the individual subunits in the proteasome. The topography shows that for the trypsin-like, the chymotrypsin-like, and the postglutamyl cleaving activities, the pairs of ␤ type subunits, which are thought to form active sites, are nearest neighbors.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Subunit arrangement in the human 20S proteasome

Köpp

Hendil

Dahlmann

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

110

View full text Add to dashboard Cite

show abstract

“…In eukaryotes, however, prosequences are longer and more heterogeneous 123,124 and only three subunits (PRE2, PRE3, and PUB1) of the seven distinct β-subunits of the yeast proteasome are processed and become catalytically active. [107][108][109]125 Similarly, X, Y, and Z β-subunits of mammalian proteasome are catalytically active. The processing event appears to be autocatalytic as in other Ntn hydrolases 117 and coupled to proteasome assembly.…”

Section: B 20s and 26s Proteasome: Converging Points Of Ubiquitinatementioning

confidence: 99%

The ubiquitin‐proteasome pathway and proteasome inhibitors

Myung

Kim

Crews

2001

Medicinal Research Reviews

395

252

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The ubiquitin-proteasome pathway has emerged as a central player in the regulation of several diverse cellular processes. Here, we describe the important components of this complex biochemical machinery as well as several important cellular substrates targeted by this pathway and examples of human diseases resulting from defects in various components of the ubiquitin-proteasome pathway. In addition, this review covers the chemistry of synthetic and natural proteasome inhibitors, emphasizing their mode of actions toward the 20S proteasome. Given the importance of proteasomemediated protein degradation in various intracellular processes, inhibitors of this pathway will continue to serve as both molecular probes of major cellular networks as well as potential therapeutic agents for various human diseases.

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“…The "trypsin-like" activity cleaves substrates after basic residues and the "peptidyl-glutamyl peptide hydrolytic" (PGPH) or "caspase-like" activity cleaves after acidic residues (13,14). These primary hydrolytic activities have been linked through mutagenesis and inhibitor studies to three catalytically active ␤ subunits: ␤1, ␤2, and ␤5 (15). These studies have assigned the chymotryptic activity to ␤5, the tryptic activity to ␤2, and the PGPH activity to ␤1 (16).…”

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confidence: 99%

Biochemical Analysis of the 20 S Proteasome of Trypanosoma brucei

Wang

Bozdech

Liu

et al. 2003

Journal of Biological Chemistry

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We describe here biochemical characterization of the 20 S proteasome from the parasitic protozoan Trypanosoma brucei. Similar to the mammalian proteasome, the T. brucei proteasome is made up of seven ␣-and seven ␤-subunits. Of the seven ␤-type subunits, five contain pro-sequences that are proteolytically removed during assembly, and three of them are predicted to be catalytic based on primary sequence. Affinity labeling studies revealed that, unlike the mammalian proteasome where three ␤-subunits were labeled by the affinity reagents, only two ␤-subunits of the T. brucei proteasome were labeled in the complex. These two subunits corresponded to ␤2 and ␤5 subunits responsible for the trypsin-like and chymotrypsin-like proteolytic activities, respectively. Screening of a library of 137,180 tetrapeptide fluorogenic substrates against the T. brucei 20 S proteasome confirmed the nominal ␤1-subunit (caspase-like or PGPH) activity and identified an overall substrate preference for hydrophobic residues at the P1 to P4 positions in a substrate. This overall stringency is relaxed in the 11 S regulator (PA26)-20 S proteasome complex, which shows both appreciable activities for cleavage after acidic amino acids and a broadened activity for cleavage after basic amino acids. The 20 S proteasome from T. brucei also shows appreciable activity for cleavage after P1-Gln that is minimally observed in the human counterpart. These results demonstrate the importance of substrate sequence specificity of the T. brucei proteasome and highlight its biochemical divergence from the human enzyme.

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PRE3, highly homologous to the human major histocompatibility complex‐linked LMP2 (RING12) gene, codes for a yeast proteasome subunit necessary for the peptidylglutamyl‐peptide hydrolyzing activity

Cited by 80 publications

References 37 publications

Subunit arrangement in the human 20S proteasome

Subunit arrangement in the human 20S proteasome

The ubiquitin‐proteasome pathway and proteasome inhibitors

Biochemical Analysis of the 20 S Proteasome of Trypanosoma brucei

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