Disease relevance of PRPF6

• Mutational inactivation of the mouse Ant1 gene resulted in myopathy, cardiomyopathy, and multiple mtDNA deletions in association with elevated reactive oxygen species (ROS) production [1].
• RT-PCR was used to measure the mRNA levels of three important mitochondrial proteins; NADH-ubiquinone-oxireductase subunit 4L(ND-4L), subunit C of the F1F0-ATP synthase (SUC), and adenine nucleotide translocator 1 (ANT1) in IUGR and control rats in fetal and juvenile life [2].
• This study explored the role of adenine nucleotide translocator-1 (ANT1) in cardiomyocyte apoptosis during left ventricular hypertrophy (LVH) that developed in response to pressure overload [3].
• Recently, the A114P missense mutation in the human Ant1 protein was found to be associated with autosomal dominant progressive external ophthalmoplegia (adPEO) [4].
• Autosomal dominant external ophthalmoplegia and bipolar affective disorder associated with a mutation in the ANT1 gene [5].

High impact information on PRPF6

• Separate translocases in the mitochondrial outer membrane (TOM complex) and in the inner membrane (TIM complex) facilitate recognition of preproteins and transport across the two membranes [6].
• Proteins that are destined for the matrix of mitochondria are transported into this organelle by two translocases: the TOM complex, which transports proteins across the outer mitochondrial membrane; and the TIM23 complex, which gets them through the inner mitochondrial membrane [7].
• The biogenesis of TOM is of special interest because the complex is required for its own biogenesis [8].
• A multisubunit translocase of the outer mitochondrial membrane (TOM complex) mediates both the import of mitochondrial precursor proteins into the internal compartments of the organelle and the insertion of proteins residing in the mitochondrial outer membrane [9].
• Thus, hPrp31 and hPrp6 form an essential connection between the U4/U6 and U5 snRNPs in vivo [10].

Chemical compound and disease context of PRPF6

• For advanced colorectal carcinoma, two new drugs, raltitrexed (TOM) and oxaliplatin (L-OHP), have recently shown interesting results [11].
• Among the factors evaluated with multivariate analysis, sex, age, PS, creatinine clearance, previous chemotherapy treatment, presence of liver metastases and oncology centre were not significantly associated with TOM hepatotoxicity [12].

Biological context of PRPF6

• The ANT-1 was identical to a binding protein of human splicing factor U5 snRNP (U5 snRNP-associated protein) [13].
• Aortic blood pressure (ABP), LVH, myocardial apoptosis index (MAI), and ANT1 mRNA expression were quantified in 7 subgroups of 3 treated and 3 control rats that were killed, respectively, at 1, 2, 4, 7, 14, 21, or 30 days post-surgery [3].
• Autosomal dominant progressive external ophthalmoplegia (adPEO) is caused by mutations in at least three different genes: ANT1 (chromosome 4q34-35), TWINKLE, and POLG [14].
• A novel ANT1 gene mutation with probable germline mosaicism in autosomal dominant progressive external ophthalmoplegia [15].
• Biogenesis of the mitochondrial TOM complex [8].

Anatomical context of PRPF6

• The ANT-1 sequence was identical to that of a protein that binds to U5 small nuclear ribonucleoprotein particle, a human homologue of yeast splicing factor Prp6p, involved in spliceosome [16].
• In these experiments, IL-1 was given to rats intraventricularly and sacrificed 2 h later; both CBP and ANT-1 transcripts were upregulated in the cerebral cortex and hypothalamus [17].
• In treated rats, the expression of ANT1 mRNA in myocardium was up-regulated at 4 days, peaked at 7 days, and returned to control levels at 14 days post-surgery [3].
• We found that of its components, only the voltage-dependent anion channel in the outer mitochondrial membrane and the adenine nucleotide translocator-1 (ANT-1), a PT-pore subunit of the inner membrane, are apoptosis inducers [18].
• EOMs of wild-type mice exhibited higher levels of Ant2 mRNA compared with hindlimb muscle, which may compensate for the Ant1 loss in mutant mouse EOMs and account for the normal EOM function [19].

Associations of PRPF6 with chemical compounds

• In contrast, the ANT-1 did not enhance any ligand-dependent AF-2 activities [16].
• The resulting leucine to proline substitution likely modifies the secondary structure of the ANT1 protein [14].
• We report a novel heterozygous C to A transversion at nucleotide 269 in the ANT1 gene in a German family with PEO, predicted to convert a highly conserved alanine at codon 90 to aspartic acid [15].
• Blue native polyacrylamide gel electrophoresis of digitonin-solubilized outer membranes revealed that 1C9-2 is firmly associated with TOM40 in the approximately 400-kDa complex, with a size and composition similar to those of the fungal TOM core complex [20].
• The ability of herbimycin A to sensitize K562, TOM 1 or KCL-22 cells to apoptosis induction correlated with its ability to decrease the cellular content of phosphotyrosyl proteins in these Philadelphia-positive lines [21].

Analytical, diagnostic and therapeutic context of PRPF6

• Sequence analysis and linkage analysis showed that ANT1 was not the primary genetic cause of Sengers syndrome [22].
• By using a bacterial two-hybrid assay and crosslinking strategies, we have identified TOM22, a component of the translocase of the outer mitochondrial membrane (TOM), as a mitochondrial receptor of Bax [23].
• Elevated baseline transaminase levels (p=0.001), number of chemotherapy cycles (p<0.001), TOM cumulative dose (p=0.018), unprolonged intervals between courses (p<0.001) and TOMOX regimen (p<0.001) emerged as factors predictive of hepatotoxicity [12].
• From the profiles of % CF leakage, together with measurements of differential scanning calorimetry, it was found that hydrophobic DOM-beta-CD penetrates the matrix of the liposomes to interact with them as well as TOM-beta-CD, and that less hydrophobic alpha-CD exists at the surface of the membrane to interact with the liposomes [24].
• The Traditional Oriental Medicine Database (TradiMed 2000 DB) is a unique database of traditional Oriental herbal therapy containing a variety of information such as formulae, chemical information on ingredients, botanical information on herbal materials, and a dictionary of disease classification (TOM and Western classification) [25].

References