Regulatory mechanisms of hypoxia-inducible factor 1 activity: Two decades of knowledge.
Cancer Sci
; 109(3): 560-571, 2018 Mar.
Article
em En
| MEDLINE
| ID: mdl-29285833
ABSTRACT
Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator of various genes related to cellular adaptive responses to hypoxia. Dysfunctions in the regulatory systems of HIF-1 activity have been implicated in the pathogenesis of various diseases including malignant tumors and, thus, elucidating the molecular mechanisms underlying the activation of HIF-1 is eagerly desired for the development of novel anti-cancer strategies. The importance of oxygen-dependent and ubiquitin-mediated proteolysis of the regulatory subunit of HIF-1 (HIF-1α) was first reported in 1997. Since then, accumulating evidence has shown that HIF-1α may become stable and active even under normoxic conditions; for example, when disease-associated genetic and functional alterations in some genes trigger the aberrant activation of HIF-1 regardless of oxygen conditions. We herein review the last two decades of knowledge, since 1997, on the regulatory mechanisms of HIF-1 activity from conventional oxygen- and proteolysis-dependent mechanisms to up-to-the-minute information on cancer-associated genetic and functional alteration-mediated mechanisms.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator 1 Induzível por Hipóxia
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Cancer Sci
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão