Identification and Functional Analysis of the Rat Caspase-3 Gene Promoter
Autor: | Wenfang Liu, Geping Wang, Alexander G. Yakovlev |
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Rok vydání: | 2002 |
Předmět: |
Transcription
Genetic Sp1 Transcription Factor Molecular Sequence Data Response element Biology Transfection PC12 Cells Biochemistry Proto-Oncogene Protein c-ets-1 Transcription (biology) Proto-Oncogene Proteins Sequence Homology Nucleic Acid Animals Humans Cloning Molecular Binding site Luciferases Promoter Regions Genetic Molecular Biology Gene Transcription factor Cell Nucleus Sp1 transcription factor Binding Sites Base Sequence Proto-Oncogene Proteins c-ets Caspase 3 Reverse Transcriptase Polymerase Chain Reaction Effector Brain Promoter Plicamycin Cell Biology Molecular biology Intercalating Agents Rats Caspases Cell Division Gene Deletion HeLa Cells Protein Binding Transcription Factors |
Zdroj: | Journal of Biological Chemistry. 277:8273-8278 |
ISSN: | 0021-9258 |
DOI: | 10.1074/jbc.m110768200 |
Popis: | Caspase-3 is the major effector in apoptosis triggered by various stimuli. Previous studies demonstrated a significant increase in transcriptional activity of the caspase-3 gene during neuronal apoptosis. Recent findings suggest that differential expression of the caspase-3 gene may underlie the regulation of apoptotic susceptibility during brain development and after acute injury to the mature brain. We identified and cloned the rat caspase-3 gene promoter, determined its structure, and examined its regulation during a course of apoptosis in PC12 cells. Results demonstrate that this promoter lacks a TATA-box and contains a cluster of Sp1 elements and multiple transcription start sites. The first identified transcription start site is located 87-bp upstream from the first splicing site. A role of Sp1 elements in the regulation of caspase-3 promoter activity is demonstrated by the inhibition of Sp1 binding using mithramycin A. Results of deletion analysis show that an Ets-1-like element located between nucleotides -1646 and -1632 relative to the most extended transcription start site is necessary to achieve sustained transcriptional activity. Homology analysis revealed that the 5'-flanking region of the human caspase-3 gene exhibits significant similarity to a regulatory region of the rat gene. |
Databáze: | OpenAIRE |
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