Transcription factor ZBP-89 regulates the activity of the ornithine decarboxylase promoter.
Appropriate cellular levels of polyamines are required for cell growth and differentiation. Ornithine decarboxylase is a key regulatory enzyme in the biosynthesis of polyamines, and precise regulation of the expression of this enzyme is required, according to cellular growth state. A variety of mitogens increase the level of ornithine decarboxylase activity, and, in most cases, this elevation is due to increased levels of mRNA. A GC box in the proximal promoter of the ornithine decarboxylase gene is required for basal and induced transcriptional activity, and two proteins, Sp1 and NF-ODC1, bind to this region in a mutually exclusive manner. Using a yeast one-hybrid screening method, ZBP-89, a DNA-binding protein, was identified as a candidate for the protein responsible for NF-ODC1 binding activity. Three lines of evidence verified this identification; ZBP-89 copurified with NF-ODC1 binding activity, ZBP-89 antibodies specifically abolished NF-ODC1 binding to the GC box, and binding affinities of 12 different double-stranded oligonucleotides were indistinguishable between NF-ODC1, in nuclear extract, and in vitro translated ZBP-89. ZBP-89 inhibited the activation of the ornithine decarboxylase promoter by Sp1 in Schneider's Drosophila line 2, consistent with properties previously attributed to NF-ODC1.
Law
G L
GL
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Itoh
H
H
Law
D J
DJ
Mize
G J
GJ
Merchant
J L
JL
Morris
D R
DR
D001665:Binding Sites / Q000235:genetics; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000032:analysis; D009955:Ornithine Decarboxylase / Q000235:genetics*; D011073:Polyamines / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011073:Polyamines; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; C110951:ZNF148 protein, human; D009955:Ornithine Decarboxylase