Open AccessILKAP Binding to and Dephosphorylating HIF-1α is Essential for Apoptosis Induced by Severe Hypoxia
Author(s) -
Tielong Liu,
Yonggang Liu,
Jiantao Cao,
Xīn Gào,
Jing Wang,
Guanghui Chen,
Yang Wang,
Ge Liu,
Guangjian Bai,
Yiwei Hu,
Jiaxiang Yang,
Lianfeng Dong,
Xinbao Quan,
Weiwei Zou
Publication year - 2018
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000489656
Subject(s) - dephosphorylation , apoptosis , phosphatase , phosphorylation , viability assay , microbiology and biotechnology , biology , kinase , protein phosphatase 2 , hypoxia inducible factors , chemistry , biochemistry , gene
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.