Identity of GABP with NRF-2, a multisubunit activator of cytochrome oxidase expression, reveals a cellular role for an ETS domain activator of viral promoters.
The ETS domain proteins are a diverse family of transcriptional activators that have been implicated recently in the expression of a number of cell-specific and viral promoters. Nuclear respiratory factor 2 (NRF-2) is a nuclear transcription factor that activates the proximal promoter of the rat cytochrome c oxidase subunit IV (RCO4) gene through tandem sequence elements. These elements conform to the consensus for high-affinity ETS domain recognition sites. We have now purified NRF-2 to homogeneity from HeLa cells and find that it consists of five polypeptides, only one of which has intrinsic DNA-binding ability. The others participate in the formation of heteromeric complexes with distinct binding properties. NRF-2 also specifically recognizes multiple binding sites in the mouse cytochrome c oxidase subunit Vb (MCO5b) gene. As in the functionally related RCO4 gene, tandemly arranged NRF-2 sites are essential for the activity of the proximal MCO5b promoter, further substantiating a role for NRF-2 in respiratory chain expression. Determination of peptide sequences from the various subunits of HeLa NRF-2 reveals a high degree of sequence identity with mouse GA-binding protein (GABP), a multisubunit ETS domain activator of herpes simplex virus immediate early genes. A cellular role in the activation of nuclear genes specifying mitochondrial respiratory function is thus assigned to an ETS domain activator of viral promoters.
Department of Cell, Molecular, and Structural Biology, Northwestern University Medical School, Chicago, Illinois 60611.
J V
JV
Virbasius
C A
CA
Virbasius
R C
RC
Scarpulla
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics*; D051268:GA-Binding Protein Transcription Factor; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D051381:Rats; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D018139:Simplexvirus / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D051268:GA-Binding Protein Transcription Factor; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D004247:DNA; D003576:Electron Transport Complex IV; D015500:Chloramphenicol O-Acetyltransferase