Characterization of ZBP-SO, a Novel Zinc-Finger Binding Protein
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Authors
Livingston, Cynthia
Issue Date
1999
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
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.
Description
vi, 18 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.