Transcription Factor ZBP-89 Regulates the Activity of the Ornithine Decarboxylase
Promoter
G. Lynn Law, Hideaki Itoh, David J. Law, Gregory J. Mize, Juanita L. Merchant
and David R. Morris
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 twelve 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.