Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA sequences required for expression of the mouse cytochrome c oxidase subunit IV (COXIV) promoter were identified by transient expression of recombinant COXIV-chloramphenicol acetyltransferase constructs in COS and NIH-3T3 cells. Activity of the COXIV promoter is shown to depend upon upstream Sp1 binding sequences and two tandemly repeated 21-base pair sequence elements each mapping to sites of mRNA initiation. Each initiation region repeat contains a binding site for an ets-related transcription factor which demonstrates specificity for the characteristic GGAA ets sequence motif and reactivity with an ets domain-directed monoclonal pan ets antibody. The two 21-base pair repeats are sufficient for transcriptional activity suggesting that the ets-related factor may be involved in both transcriptional activation and start site positioning. The ets-related protein found in COS nuclear extracts is shown to be identical or closely related to the GA-binding protein (GABP) by comparison of electrophoretic mobilities and immunological reactivities of DNA-protein complexes formed with purified recombinant expressed GABP alpha and beta subunits. Sp1 and the GABP-related factors also bind to another mouse cytochrome oxidase subunit gene COXVb. The similar promoter features of these two genes suggests a possible means of coordinate transcriptional regulation among such respiratory proteins.
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PMID:The basal promoter elements of murine cytochrome c oxidase subunit IV gene consist of tandemly duplicated ets motifs that bind to GABP-related transcription factors. 133 Oct 86

Cytochrome c oxidase (COX, EC 1.9.3.1), the last component of the mitochondrial electron transfer chain, is built up by 13 polypeptides; 3 of them are encoded by the mitochondrial genome while the 10 smaller subunits are encoded by the nuclear genome. Several nuclear-encoded subunits occur in two different tissue-specific isoforms, a constitutive "L"-form and an "M"-form specific for skeletal and heart muscle. In this article, we describe the genomic sequence and organization of the human gene for COX subunit VIIa-M (COX7A1) located on chromosome 19q13.1 and compare it to its bovine homologue. The coding region of the gene extends over 1.45 kb of genomic sequence, organized in four exons. Intron-exon boundaries are well conserved between cattle and humans. Although it is a gene for a tissue-specific isoform, it has some features of a housekeeping gene: it is located in a CpG island, like its bovine homologue, and no TATA or CCAAT boxes were found in the 5' flanking sequence. Southern hybridization of COX7A1 to human genomic DNA revealed no pseudogenes. Putative binding sites for ubiquitous transcription factors like Sp1 and specific expression in skeletal as well as in heart muscle have been found. In contrast to the bovine gene, the human gene contains putative binding sites for nuclear respiratory factor 2 (NRF-2), which is implicated in the activation of other respiratory enzymes. Therefore, the human and the bovine genes, although well conserved in their coding regions, could differ in the tissue-specific regulation of gene expression. Knowledge of the gene structure will facilitate the analysis of the involvement of subunit VIIa in mitochondrial myopathies and may provide clues to the function of this subunit in a multicomponent enzyme.
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PMID:Genomic sequence and organization of the human gene for cytochrome c oxidase subunit (COX7A1) VIIa-M. 934 74

We used expression and reporter gene analysis to understand how changes in transcription factors impinge on mitochondrial gene expression during myogenesis of cultured murine myoblasts (C2C12 and Sol8). The mRNA levels for nuclear respiratory factor-1 (NRF-1) and NRF-2alpha increased 60% by the third day of myogenesis, whereas NRF-1 and NRF-2 reporter gene activity increased by fivefold over the same period. Although peroxisome proliferator activated receptor (PPARalpha) mRNA levels increased almost 10-fold, the activity of a PPAR reporter was unchanged during myogenesis. The PPAR coactivator PPAR-gamma coactivator-1alpha (PGC1alpha), a master controller of mitochondrial biogenesis, was not expressed at detectable levels. However, the mRNA for both PGC1alpha-related coactivator and PGC1beta was abundant, with the latter increasing by 50% over 3 days of differentiation. We also conducted promoter analysis of the gene for citrate synthase (CS), a common mitochondrial marker enzyme. The proximal promoter ( approximately 2,100 bp) of the human CS lacks binding sites for PPAR, NRF-1, or NRF-2. Deletion mutants, a targeted mutation, and an Sp1 site-containing reporter construct suggest that changes in Sp1 regulation also participate in mitochondrial biogenesis during myogenesis. Because most mitochondrial genes are regulated by PPARs, NRF-1, and/or NRF-2, we conducted inhibitor studies to further support the existence of a distinct pathway for CS gene regulation in myogenesis. Although both LY-294002 (a phosphatidylinositol 3-kinase inhibitor) and SB-203580 (a p38-MAPK inhibitor) blocked myogenesis (as indicated by creatine phosphokinase activity), only SB-203580 prevented the myogenic increase in cytochrome oxidase activity, whereas only LY-294002 blocked the increase in CS (enzyme and reporter gene activities). Collectively, these studies help delineate the roles of some transcriptional regulators involved in mitochondrial biogenesis associated with myogenesis and underscore an import role for posttranscriptional regulation of transcription factor activity.
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PMID:Control of mitochondrial biogenesis during myogenesis. 1653 67