Role of the human Y box-binding protein YB-1 in cellular sensitivity to the DNA-damaging agents cisplatin, mitomycin C, and ultraviolet light.
Cancer Res
; 56(18): 4224-8, 1996 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-8797596
ABSTRACT
The Y box-binding protein (YB-1) binds to DNA sequences, present in the control regions of many genes, that contain an inverted CCAAT box. The binding activity of a nuclear factor, designated MDR-NF1, to an inverted CCAAT box in the promoter of the multidrug resistance 1 (MDR1) gene has previously been shown to be increased in nuclear extracts of cells exposed to UV radiation or various anticancer agents. The MDR-NF1 cDNA has now been cloned by screening a human colon library with an active fragment of the MDR1 promoter. The amino acid sequence encoded by the cloned cDNA was identical to that of YB-1. Northern blot analysis revealed that YB-1 mRNA was present in all human tissues examined. Rabbit antibodies were generated against synthetic peptides corresponding to YB-1, and indirect immunofluorescence microscopy with these antibodies showed that the concentration of YB-1 in all cisplatin-resistant cell lines examined was higher than that in the respective drug-sensitive parental cells. Transfection of human epidermoid cancer KB cells with a YB-1 antisense construct established two cell lines with reduced concentrations of YB-1. These transfectants showed increased sensitivity to cisplatin, mitomycin C, and UV radiation but not to vincristine, doxorubicin, camptothecin, or etoposide. Thus, YB-1 may protect cells from the cytotoxic effects of agents that induce cross-linking of DNA, suggesting a novel function of this ancestor DNA-binding protein.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Raios Ultravioleta
/
Dano ao DNA
/
Cisplatino
/
Mitomicina
/
Resistência a Múltiplos Medicamentos
/
Proteínas Estimuladoras de Ligação a CCAAT
/
Proteínas de Ligação a DNA
/
Antineoplásicos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Japão