Disease relevance of RPN11

• Escherichia coli cells expressing ppr1(+), like ones expressing MPR1, were resistant to AZC and produced an AZC acetyltransferase [1].
• The MPR1 gene coding sequence driven by two different constitutive promoters, with or without the 5'- and 3'-noncoding sequence from the MPR1 gene adjacent to the conventional NOS terminator, was transformed into tobacco ( Nicotiana tabacum L. cv. Xanthi) plants via Agrobacterium tumefaciens infection [2].

High impact information on RPN11

• Yeast proteasomes contain two deubiquitinating enzymes, Ubp6 and Rpn11 [3].
• We provide evidence that RPN11 functions downstream of RAS2, and show that mutation of two additional proteasome subunits results in identical phenotypes [4].
• We show that RPN11, a gene encoding a subunit of the regulatory cap of the proteasome, is required for UV-stimulated activation of Gcn4p target genes, but is dispensable for their activation by the general control pathway [4].
• Role of the yeast acetyltransferase Mpr1 in oxidative stress: regulation of oxygen reactive species caused by a toxic proline catabolism intermediate [5].
• In contrast, overexpression of MPR1 leads to an increase in cell viability and a decrease in ROS level after oxidative treatments [5].

Biological context of RPN11

• Nevertheless, these rpn11 mutants suppress the mitochondrial phenotypes associated with mpr1-1 by intragene complementation [6].
• A mutation in a novel yeast proteasomal gene, RPN11/MPR1, produces a cell cycle arrest, overreplication of nuclear and mitochondrial DNA, and an altered mitochondrial morphology [7].
• We recently have discovered, on the chromosome of Saccharomyces cerevisiae Sigma1278b, a novel gene MPR1 required for the resistance of Sigma1278 background strains to toxic AZC [8].
• Mpr1p was considered to be a member of the N-acetyltransferase superfamily based on the results of an Ala-scan mutagenesis through the highly conserved region involved in binding acetyl-CoA in members of the superfamily [8].
• Gene expression and enzymatic analysis showed that the cloned Spa MPR1 gene encodes an L-azetidine-2-carboxylic acid acetyltransferase of 231 amino acids, which has 87% identity to the MPR1 protein [9].

Anatomical context of RPN11

• Localization of the Rpn11p/Mpr1p protein has been studied by green fluorescent protein fusion, and the fusion protein has been found to be mainly associated to cytoplasmic structures [7].

Associations of RPN11 with chemical compounds

• Since the mutant strain is thermosensitive both on glucose and on glycerol, we searched for revertants in order to shed light on the Rpn11/Mpr1 functions [10].
• In vitro studies with bacterially expressed Mpr1 demonstrated that Mpr1 can acetylate P5C, or, more likely, its equilibrium compound glutamate-gamma-semialdehyde, at neutral pH [5].
• When this novel MPR1 or MPR2 gene (sigma 1278b gene for L-proline analogue resistance) was introduced into the other S. cerevisiae strains, all of the recombinants were resistant to L-azetidine-2-carboxylic acid, indicating that both MPR1 and MPR2 are expressed and have a global function in S. cerevisiae [11].
• The kanamycin-selected transgenic plants with a high level of Mpr1 activity grew normally, and their progeny expressed acetyltransferase activity that could utilize A2C, azetidine-3-carboxylic acid and 4-hydroxy- l-proline as substrates [2].

Other interactions of RPN11

• STS1 also interacted with the second suppressor, RPN11, a subunit of the 26S proteasome, in the two-hybrid system [12].
• CSN6 haploinsufficiency restored growth, whereas reduction of proteasome subunits RPN8 or RPN11 had no effect [13].
• Recent studies have revealed that similar metalloprotease motifs--JAMMs--in the Rpn11 subunit of the 26S proteasome lid and in the Csn5 subunit of the COP9 signalosome are involved in deubiquitination and deneddylation, respectively [14].
• First, overexpression of two components of the 19 S RP, namely Pad1/Rpn11 and Mts3/Rpn12, rescued the temperature-sensitive growth defect of the dss1 mutant [15].

Analytical, diagnostic and therapeutic context of RPN11

• Further, genomic PCR analysis showed that most of the S. cerevisiae complex spp. have the sequence highly homologous to the MPR1 gene [9].

References