The requirement of c-Jun N-terminal kinase 2 in regulation of hypoxia-inducing factor-1α mRNA stability.
J Biol Chem
; 287(41): 34361-71, 2012 Oct 05.
Article
em En
| MEDLINE
| ID: mdl-22910906
ABSTRACT
The mRNA of hif-1α is considered as being constitutively and ubiquitously expressed, regardless of the level of oxygen tension. However many recent reports have showed that hif-1α mRNA could be regulated by natural antisense transcripts, potential microRNAs, and low O(2). In this study, it was found that a deficiency of JNK2 expression reduced HIF-1α protein induction in response to nickel treatment resulting from the impaired expression of hif-1α mRNA. Both the promoter luciferase assay and mRNA degradation assay clearly showed that depletion of JNK2 affected stability of hif-1α mRNA, rather than regulated its transcription. In addition, nucleolin, a classic histone chaperone, was demonstrated to physically bind to hif-1α mRNA and maintain its stability. Further investigation indicated that JNK2 regulated nucleolin expression and might in turn stabilize hif-1α mRNA. Collectively, we provided one more piece of evidence for the oncogenic role of JNK2 and nucleolin in regulating the cancer microenvironments by controlling HIF-1α expression.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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RNA Mensageiro
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Regulação da Expressão Gênica
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Proteínas de Ligação a RNA
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Estabilidade de RNA
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Proteína Quinase 9 Ativada por Mitógeno
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Subunidade alfa do Fator 1 Induzível por Hipóxia
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos