Regulation of the catalase gene promoter by Sp1, CCAAT-recognizing factors, and a WT1/Egr-related factor in hydrogen peroxide-resistant HP100 cells.
Cancer Res
; 61(15): 5885-94, 2001 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-11479230
ABSTRACT
Reactive oxygen species play a critical role in the onset of apoptosis induced by various extracellular stimuli, including ionizing radiation. Therefore active regulation of reactive oxygen species-metabolizing enzymes may be one response to an apoptotic stimulus. In this regard, HP100 cells, H(2)O(2)-resistant variants derived from human leukemia HL60 cells, display an interesting phenotype in which the activity of catalase is constitutively high, whereas its mRNA is reduced after X-ray irradiation. In the present study, we investigated the molecular mechanisms underlying this phenomenon. By combining analyses from nuclear run-on, reporter gene transient transfection, genomic footprinting, site-directed mutagenesis, electrophoretic mobility shift analysis, and Western blotting experiments, we found that constitutively elevated catalase expression is strongly regulated at the transcriptional level by both Sp1 and CCAAT-recognizing factors and that much higher levels of nuclear Sp1 and NF-Y are present in HP100 nuclei as compared with HL60 nuclei. In addition, we demonstrated an X-ray-inducible association of a WT1/Egr-related factor with an overlapping Sp1/Egr-1 recognition sequence located within the core promoter of the catalase gene. This association may lead to inactivation of the promoter by disturbing or competing with the transactivating ability of Sp1.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Catalase
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Regulação Enzimológica da Expressão Gênica
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Regulação Leucêmica da Expressão Gênica
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Fator de Transcrição Sp1
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Proteínas Imediatamente Precoces
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Fator de Ligação a CCAAT
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Proteínas de Ligação a DNA
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Peróxido de Hidrogênio
Limite:
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Japão