High impact information on Abcd3

• The association of nsL-TP with peroxisomal enzymes was investigated in cells by measuring fluorescence resonance energy transfer (FRET) between the microinjected Cy3-pre-nsL-TP and Cy5-labeled antibodies against the peroxisomal enzymes acyl-CoA oxidase, 3-ketoacyl-CoA thiolase, bifunctional enzyme, PMP70 and catalase [1].
• Thus peroxisome proliferators enhance the expression of the genes for both the membrane protein PMP68 and the matrix protein PBP, but the regulation of this expression appears to be mediated by different mechanisms [2].
• Similarly, BM 15766 and Wy-14,643 increased transcription of the PMP68 gene in vitro, whereas PBP gene transcription was increased by Wy-14,643 but not by BM 15766 [2].
• The kinetics and sequence of induction of PMP68 and PBP following a single dose of Wy-14,643 were compared and shown to be similar, and the effects were reversible [2].
• Dietary clofibrate, di-2-(ethylhexyl)phthalate and Wy-14,643, three structurally unrelated proliferators, all increased the mRNA and protein content of PMP68 approx. 2-fold, whereas PBP was induced 8-13-fold [2].

Biological context of Abcd3

• Analysis of the promoter sequences revealed a cryptic nuclear hormone receptor response element of the DR+4 type in the ALDR promoter and a novel 18-bp sequence motif present only in the 5' flanking DNA of the ALDR and PMP70 genes [3].
• Amino acid substitutions are clustered in both PMP22 and PMP70 genes, and their pattern supports membrane topologies derived from hydropathy profiles [4].
• It is conceivable that reduction of PMP70 might underlie decrease in peroxisomal functions and increase in oxidative stress that is well documented in this animal model [5].

Anatomical context of Abcd3

• The different expression patterns could explain why beta-oxidation is defective in X-ALD, although ALDRP and PMP70 can replace ALDP functionally in fibroblasts [3].
• We have isolated and sequenced a cDNA which encodes 376 amino acids toward the carboxy-terminus, and encompassing the putative nucleotide binding fold, of PMP68 (mouse liver peroxisomal integral membrane protein of 68 kDa) the major integral membrane protein of mouse liver peroxisomes [6].
• At pre-symptomatic 20 weeks and symptomatic 32 weeks, PMP70 was reduced in the cytoplasm of motor neurons in Tg animals and increased in glial cells in anterior horn at late age [5].
• Peroxisomal membrane protein 70 (PMP70) and Cu/Zn superoxide dismutase (SOD1) were examined in the spinal cords of transgenic (Tg) mice expressing a human mutant SOD1 protein (G93A) and their age-matched controls at 8, 20 and 32 weeks by immunohistochemistry [5].

Associations of Abcd3 with chemical compounds

• Dietary fenofibrate had no effect on the ALD and P70R genes, but strongly increased expression of the ALDR and PMP70 genes in mouse liver [3].

Other interactions of Abcd3

• Northern blot analysis identifies single mRNAs of 4.6 kb (PMP70), 1.4 kb (PMP22), and 2.3 kb (catalase) in several rodent tissues [4].
• Mouse liver PMP70 and ALDP: homomeric interactions prevail in vivo [7].

Analytical, diagnostic and therapeutic context of Abcd3

• Peroxisomal membrane protein PMP68 of mouse liver: cloning of a cDNA encompassing the nucleotide binding fold and epitope mapping of monoclonal antibodies to the expressed protein [6].

References