Characterization of ZBP-SO, a Novel Zinc-Finger Binding Protein

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Livingston, Cynthia
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Gastrin and ornithine decarboxy lase (OD) are both important enzymes in the regulation of cellular growth. Regulation of their gene's promoter regions would thereby indirectly regulate cellular proliferation. The gastrin and ODC genes both have a GC-rich promoter to which Sp1 and ZBP-89, a novel zinc finger binding protein, competitively bind. Sp1 is known to activate gastrin and ODC transcription, inducing cellular growth. ZBP-89, on the other hand, represses both promoters. This repression of the promoters indirectly regulates proliferation of the cells. By controlling the production of gastric acid, the gastrin gene also plays an important role in the gastrointestinal tract. Gastrin is normally expressed in the gastric antrum and anterior portion of the duodenum in adults and in the pancreas in the fetus. Furthermore, it is found to be overexpressed in islet cell tumors in multiple endocrine neoplasm type 1 (MEN-1) syndrome. The ODC protein catalyzes one step in the synthesis of polyamines, causing cellular growth. Overproduction of the ODC protein causes cellular proliferation and leads to some cancers. Overexpression of Sp1 and/ or underexpression of ZBP-89 may therefore lead to some types of cancers. Recently a second member of the zinc finger binding protein family was found to bind to the ODC promoter, the structure of which has striking similarities to ZBP-89 in the zinc finger region of the protein. This second protein is only 50 kD and so named ZBP-50. The purpose of this study is to map and sequence ZBP-50. ZBP-50 was mapped to chromosome lq32.1, a different loci from ZBP-89, suggesting that it is a family member of the zinc finger binding proteins rather than an alternative splice product of ZBP-89. ZBP-50 was also cloned and two thirds of it sequenced with most of the three prime sequence already finished. Functional assays suggest that ZBP-50 regulates gastrin in much the same way as ZBP-89 and therefore may also be an important contributor to some cancers.
vi, 18 p.
Kalamazoo College
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