Disease relevance of PRE2

• Pseudomonas aeruginosa PRG-1, an isolate from oil-contaminated soil, degrades benzothiophene (BT) and other related compounds in a 5% oil-basal medium system [1].

High impact information on PRE2

• The likely nucleophile for these sites is provided by the N-terminal threonine of mature Doa3 [2].
• We show that the N-terminal propeptide is required for Doa3 incorporation into the proteasome and, remarkably, that the propeptide functions in trans, suggesting it serves a chaperone-like function in proteasome biogenesis [2].
• The proforms of three of the seven different beta-type subunits, beta1/PRE3, beta2/PUP1 and beta5/PRE2, are cleaved between the threonine at position 1 and the last glycine of the pro-sequence, with release of the active-site residue Thr 1 [3].
• In rDNA, SIR2 is required for a more closed chromatin structure in two regions: SRR1, the major SIR-Responsive Region in the non-transcribed spacer, and SRR2, in the 18S rRNA coding region [4].
• We demonstrate here that Doa3 and Doa5, two essential components of the DOA pathway, are subunits of the proteasome [5].

Biological context of PRE2

• This gene is unique on the yeast genome and was located close to RPC40 and PRE2 on the right arm of chromosome XVI [6].
• Unexpectedly, we found that the yeast Doa3 and Pre3 subunits are synthesized as precursors which are processed in a manner apparently identical to that of related mammalian proteasome subunits implicated in antigen presentation, suggesting that biogenesis of the proteasome particle is highly conserved between yeast and mammals [5].
• Unlike the Doa3 propeptide, which is crucial for proteasome assembly, the Pre3 and Pup1 propeptides are dispensable for cell viability and proteasome formation [7].
• Mutations in PRG1, a yeast proteasome-related gene, cause defects in nuclear division and are suppressed by deletion of a mitotic cyclin gene [8].
• Importantly, deletion of CLB2, a gene encoding a mitotic cyclin, suppresses the temperature-sensitive growth phenotype of prg1 mutant strains [8].

Associations of PRE2 with chemical compounds

• The relative positions of the glycine residues, i.e., Gly57 in hCathA, Gly53 in CPW, and Gly47 in beta5/PRE2, present in the oxyanion hole of each enzyme were also highly conserved [9].
• Prediction of the mechanism of action of omuralide (clasto-lactacystin beta-lactone) on human cathepsin A based on a structural model of the yeast proteasome beta5/PRE2-subunit/omuralide complex [9].

Other interactions of PRE2

• These three beta-type subunits have inhibitor-binding sites, indicating that PRE2 has a chymotrypsin-like and a trypsin-like activity and that PRE3 has peptidylglutamyl peptide hydrolytic specificity [3].
• In yeast MATa cells lacking the endogenous Ste2p receptor, the S. macrospora PRE2 receptor facilitated all aspects of the pheromone response [10].
• The mutants show a specific reduction in the activity of the complex against peptide substrates with hydrophobic amino acids at the cleavage site and define two complementation groups, PRE1 and PRE2 [11].

References