Format

Send to

Choose Destination
Cell Physiol Biochem. 2018;46(6):2500-2507. doi: 10.1159/000489656. Epub 2018 May 5.

ILKAP Binding to and Dephosphorylating HIF-1α is Essential for Apoptosis Induced by Severe Hypoxia.

Author information

1
The Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China.
2
Taishan Medical University, Shandong province, Shanghai, China.
3
The Department of Medical Imaging Diagnosis, Changzheng Hospital, Second Military Medical University, Shanghai, China.

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.

KEYWORDS:

Apoptosis; Dephosphorylation; HIF-1α; Hypoxia; Ilkap

PMID:
29742494
DOI:
10.1159/000489656
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland
Loading ...
Support Center