Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis of the promoters of the bovine and human nuclear-encoded mitochondrial F0F1 ATP synthase alpha-subunit genes (ATPA) has identified several positive cis-acting regulatory regions that are important for basal promoter activity in human HeLa cells. We have previously determined that the binding of a protein factor, termed ATPF1, to an E-box sequence (CANNTG) located within one of these cis-acting regions is critical for transcriptional activation of the ATPA gene. In this article, we describe a second positive cis-acting regulatory element of the ATPA gene that is important for expression of the ATPA gene. We show that this cis-acting element also contains a binding site for a protein present in HeLa cells. On the basis of electrophoretic mobility shift patterns, oligonucleotide competition assays, and immunological cross-reactivity, we conclude that this protein factor is Yin-Yang 1 (YY1). Experiments carried out to examine the functional role of YY1 within the context of the ATPA promoter demonstrated that YY1 acts as a positive regulator of the ATPA gene. For example, when the YY1 binding site of the ATPA promoter was placed upstream of a reporter gene it was found to activate transcription in transient transfection assays. In addition, disruption of the YY1 binding site in the ATPA gene resulted in a loss of transcriptional activity. Furthermore, in cotransfection experiments overexpression of YY1 in trans was found to activate transcription of ATPA promoter-CAT constructs. Thus, at least two positive trans-acting regulatory factors, ATPF1 and YY1, are important for expression of the bovine and human F0F1 ATP synthase alpha-subunit genes.
 ...
PMID:Nuclear factor YY1 activates the mammalian F0F1 ATP synthase alpha-subunit gene. 888 41

The F1F0 ATP synthase is the central enzyme complex of the mitochondrial oxidative phosphorylation system synthesizing ATP from ADP and Pi. Our laboratory has been studying the transcriptional regulation of the nuclear gene that encodes the alpha-subunit of the mammalian mitochondrial ATP synthase complex (ATPA). We have previously identified an initiator element in the core promoter that plays an important role in expression of this gene. In this article, we demonstrate that ectopic expression of the transcription factor, upstream stimulatory factor 2 (USF2), transactivates the ATPA gene through this initiator element. Importantly, cotransfection of a dominant-negative USF2 mutant significantly reduces both the basal activity and the level of activation of the ATPA initiator by coexpressed USF2 demonstrating the role of endogenous USF2 proteins in this activation. We also identify several nucleotides in the ATPA initiator element that are important for both basal activity and USF2-dependent transactivation. We have also previously determined that the binding of the multifunctional regulatory protein, YY1, to this initiator element can positively regulate the ATPA gene. Here, we show that expression of YY1 together with USF2 results in a decreased level of activation of the ATPA initiator relative to expression of USF2 alone, suggesting competition between these two regulatory proteins.
 ...
PMID:Upstream stimulatory factor 2 activates the mammalian F1F0 ATP synthase alpha-subunit gene through an initiator element. 984 Aug 9

The GA-binding protein (GABP) is a ubiquitous heteromeric transcription factor implicated in the regulation of several genes involved in mitochondrial energy metabolism including subunits of cytochrome c oxidase, ATP synthase, and mitochondrial transcription factor 1 (mtTF1). GABPalpha subunit binds the PEA3/Ets binding sites (EBS), while GABPbeta contains a transcription activation domain and mediates alphabeta dimer and alpha(2)beta(2) tetramer formation essential for activation of transcription. Here we report the cloning of 2449 bp of the mouse (m) GABPalpha promoter region including 201 bp of the 5' end of the published mGABPalpha cDNA sequence. Surprisingly, sequences homologous to the 5'UTR of mouse, rat and human mitochondrial ATP synthase coupling factor 6 (ATPsynCF6) cDNAs were found165-240 bp upstream of the mGABPalpha cDNA. A search of the non-redundant nucleotide database revealed a human genomic sequence derived from chromosome 21 (21q22) bearing significant homology to the mGABPalpha/ATPsynCF6 promoter region and encompassed the entire hGABPalpha and hATPsynCF6 genes. Primer extension analysis revealed multiple transcription start sites for both mGABPalpha and mATPsynCF6 mRNAs that mapped near the published cDNA 5' ends. Sequence analysis identified several binding sites upstream of the GABPalpha cDNA sequence including sites for GABP (-86, -104, -169, -257, and -994), YY1 (-57), Sp1 (-242 and -226), and NRF1 (-5). No 'TATA' motif was identified near either the GABPalpha or ATPsynCF6 transcription start sites. The human and mouse promoters retain significant sequence identity including binding sites for several tissue-specific transcription factors. Transient transfection assays using Luciferase reporter constructs containing the intergenic region and flanking sequences confirmed that this region of DNA promotes transcription in both directions.
 ...
PMID:Isolation of a bi-directional promoter directing expression of the mouse GABPalpha and ATP synthase coupling factor 6 genes. 1116 19