ILKAP Binding to and Dephosphorylating HIF-1α is Essential for Apoptosis Induced by Severe Hypoxia.
Cell Physiol Biochem
; 46(6): 2500-2507, 2018.
Article
em En
| MEDLINE
| ID: mdl-29742494
ABSTRACT
BACKGROUND/AIMS:
Integrin-linked kinase-associated phosphatase (ILKAP), a serine/threonine phosphatase that belongs to the protein phosphatase 2C family, has a role in cell survival and apoptosis. Hypoxia-inducible factor 1α (HIF-1α) is the key transcription factor in the response to oxygen deficiency in mammals. Direct phosphorylation and dephosphorylation of HIF-1α affect its function. The present study investigated the role of ILKAP on HIF-1α dephosphorylation and cell behavior.METHODS:
HIF-1α was induced by hypoxia. Physical binding between ILKAP and HIF-1α was demonstrated by a co-immunoprecipitation assay. HIF-1α transcriptional activity was investigated using a hypoxia-response element-containing luciferase reporter plasmid. Cell viability was evaluated by a trypan blue dye exclusion assay. ILKAP function was explored by a gain and loss assay with an overexpression plasmid and shRNA infection.RESULTS:
ILKAP physically interacted with HIF-1α and induced its dephosphorylation. Both the HIF-1α-p53 interaction and apoptosis relied on ILKAP.CONCLUSION:
The results indicated that the ILKAP directly binds and dephosphorylates HIF-1α and responsible for severe hypoxia-induced cell apoptosis.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Fosfoproteínas Fosfatases
/
Subunidade alfa do Fator 1 Induzível por Hipóxia
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article