ZBP-99 Defines a Conserved Family of Transcription Factors and Regulates Ornithine Decarboxylase Gene Expression
| Autor: | Juanita L. Merchant, G. L. Law, Ming Du, D. J. Law |
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| Rok vydání: | 1999 |
| Předmět: |
Molecular Sequence Data
Biophysics Biology Ornithine Decarboxylase Biochemistry Gene Expression Regulation Enzymologic Gastrins Gene expression Tumor Cells Cultured Humans Gene family Amino Acid Sequence RNA Messenger Northern blot Cloning Molecular Promoter Regions Genetic Molecular Biology Transcription factor Gene Conserved Sequence Ornithine decarboxylase antizyme Expression vector Base Sequence Sequence Homology Amino Acid Zinc Fingers Promoter DNA Cell Biology Molecular biology DNA-Binding Proteins Repressor Proteins Chromosomes Human Pair 1 Trans-Activators Transcription Factors |
| Zdroj: | Biochemical and Biophysical Research Communications. 262:113-120 |
| ISSN: | 0006-291X |
| Popis: | Among transcription factors that regulate ornithine decarboxylase (ODC) gene expression are those that interact with GC-rich promoters, including Sp1 and ZBP-89. Sp1 functions as a transactivator and ZBP-89 as a transrepressor of both the ODC and gastrin promoters. This study reports the cloning and characterization of a second member of the ZBP family that also binds GC boxes. ZBP-99 contains four Krüppel-type zinc fingers that collectively share 91% amino acid sequence similarity and 79% sequence identity with those found in ZBP-89. In addition, there are highly conserved amino acid sequences in the carboxy-terminal segments of the two genes. In spite of their structural similarities, the two proteins are encoded at distinct loci, ZBP-89 on chromosome 3q21 and ZBP-99 on 1q32.1. The predicted open reading frame of ZBP-99 cDNA encodes a 99-kDa protein. Electrophoretic mobility shift assays showed that ZBP-99 protein specifically binds to the GC-rich promoter elements of gastrin and ODC genes. Northern blot analysis showed that a major ZBP-99 transcript of 5.6 kb is expressed ubiquitously at low levels, with elevated expression levels in placenta and in adult kidney, liver, and lymphocytes. Cotransfection of AGS gastric adenocarcinoma and HT-29 colon adenocarcinoma cells with a ZBP-99 expression construct and with an ODC reporter construct show that ZBP-99 repressed basal expression in the two cell lines by 80 and 60%, respectively. Collectively, the data suggest that ZBP-99 binds GC-rich promoters and may complement the activities mediated by ZBP-89. |
| Databáze: | OpenAIRE |
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