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

An analysis of the promoter of a bovine and human nuclear-encoded mitochondrial ATP synthase alpha-subunit gene (ATPA) revealed the presence of a positive control element. DNase I footprinting and electrophoretic mobility shift assays demonstrated that this cis-acting regulatory element contains a binding site for a protein present in human HeLa nuclei, termed ATP factor 1 (ATPF1). The ATPF1 binding site contains the sequence, CANNTG, a sequence identical to the recognition site for a family of transcription factors containing a basic region adjacent to a helix-loop-helix domain. Site-directed point mutations of the basic helix-loop-helix binding site demonstrated the critical role of this element for both binding of ATPF1 and also for transcriptional activation of the ATPA gene.
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PMID:ATPF1 binding site, a positive cis-acting regulatory element of the mammalian ATP synthase alpha-subunit gene. 812 59

We have previously identified several positive cis-acting regulatory regions in the promoters of the bovine and human nuclear-encoded mitochondrial F0F1-ATP synthase alpha-subunit genes (ATPA). One of these cis-acting regions contains the sequence 5'-CACGTG-3' (an E-box), to which a number of transcription factors containing a basic helix-loop-helix motif can bind. This E-box element is required for maximum activity of the ATPA promoter in HeLa cells. The present study identifies the human transcription factor, upstream stimulatory factor 2 (USF2), as a nuclear factor that binds to the ATPA E-box and demonstrates that USF2 plays a critical role in the activation of the ATPA gene in vivo. Evidence includes the following. Antiserum directed against USF2 recognized factors present in HeLa nuclear extracts that interact with the ATPA promoter in mobility shift assays. Wild-type USF2 proteins synthesized from expression vectors trans-activated the ATPA promoter through the E-box, whereas truncated USF2 proteins devoid of the amino-terminal activation domains did not. Importantly, expression of a dominant-negative mutant of USF2 lacking the basic DNA binding domain but able to dimerize with endogenous USF proteins significantly reduced the level of activation of the ATPA promoter caused by ectopically coexpressed USF2, demonstrating the importance of endogenous USF2 in activation of the ATPA gene.
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PMID:Regulation of the nuclear gene that encodes the alpha-subunit of the mitochondrial F0F1-ATP synthase complex. Activation by upstream stimulatory factor 2. 909 98

To identify molecules that contribute to insulin resistance, we compared the patterns of gene expression in skeletal muscle of the obese ob/ob mouse, a genetic model of obesity and severe insulin resistance, with that of its thin littermate (ob/+) using the mRNA differential display method. From about 9,000 cDNAs displayed, we found 12 differentially expressed in ob/ob mice skeletal muscle that could be recovered from the differential display gels and confirmed by Northern blot analysis and sequenced. Eight mRNAs were overexpressed in ob/ob muscle: Id2 (a negative regulator of the basic helix-loop-helix family of transcription factors), fast skeletal muscle troponin T, ribosomal protein L3, the integral protein of the peroxisomal membrane 22PMP, the mammalian homolog of geranylgeranyl pyrophosphate synthase, an mRNA related to phosphatidylinositol-glycan-specific phospholipase D, and two unknown mRNAs. The level of overexpression of these mRNAs in skeletal muscle varied from a 500% increase to as little as a 25% increase. Two mRNAs were underexpressed 20-35%, including the f-subunit of mitochondrial ATP synthase and a retrovirus-related DNA. Two proteins with multiple transcripts, skeletal muscle alpha-tropomyosin and one for a repetitive sequence, showed a change in mRNA pattern of expression in the muscle of the ob/ob mouse. Because the primary genetic defect in the ob/ob mouse is known to be in the leptin gene, these data indicate how acquired alterations in gene expression of multiple classes of proteins may play a role in the complex pathogenesis of insulin resistance in obesity and diabetes.
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PMID:Alterations in skeletal muscle gene expression of ob/ob mice by mRNA differential display. 972 34