The p14ARF tumor suppressor protein facilitates nucleolar sequestration of hypoxia-inducible factor-1alpha (HIF-1alpha ) and inhibits HIF-1-mediated transcription.
J Biol Chem
; 276(30): 28421-9, 2001 Jul 27.
Article
em En
| MEDLINE
| ID: mdl-11382768
ABSTRACT
Oncogenic alterations can influence tumor cell survival partly by affecting the activity of the hypoxia-inducible factor-1 (HIF-1) transcription factor. The alpha subunit of HIF-1 was found to be frequently overexpressed in advanced tumors, which was proposed to help the adaptation of tumor cells to hypoxia. Here we show that an important tumor suppressor protein, p14ARF (alternative reading frame product of the INK4A locus) can directly inhibit the transcriptional activity of HIF-1 by sequestering its alpha subunit into the nucleolus. The interaction requires neither p53 nor HDM2. This is one of the first reports that describe the interaction of p14ARF with a protein besides HDM2, which may define a p53-independent tumor suppressor activity for p14ARF.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Transcrição Gênica
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Proteínas Nucleares
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Proteínas
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Núcleo Celular
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Proteínas de Ligação a DNA
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA