Transcription factor ZBP-89 regulates the activity of the ornithine decarboxylase promoter

被引:75
作者
Law, GL
Itoh, H
Law, DJ
Mize, GJ
Merchant, JL
Morris, DR
机构
[1] Univ Washington, Dept Biochem, Seattle, WA 98195 USA
[2] Akita Univ, Sch Med, Dept Biochem, Akita 010, Japan
[3] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Physiol, Ann Arbor, MI 48109 USA
[5] Howard Hughes Med Inst, Ann Arbor, MI 48109 USA
关键词
D O I
10.1074/jbc.273.32.19955
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, Spl 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 co-purified 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 Spl in Schneider's Drosophila line 2, consistent with properties previously attributed to NF-ODC1.
引用
收藏
页码:19955 / 19964
页数:10
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