Oncotarget

Research Papers:

Von Hippel-Lindau regulates interleukin-32β stability in ovarian cancer cells

Hyo Jeong Yong, Jeong Su Park, Ae Lee Jeong, Sora Han, Sunyi Lee, Hye In Ka, Buyanravjkh Sumiyasuren, Hyun Jeong Joo, Su Jeong So, Ji Young Park, Do-Young Yoon, Jong Seok Lim, Myeong-Seok Lee, Hee Gu Lee and Young Yang _

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Oncotarget. 2017; 8:69833-69846. https://doi.org/10.18632/oncotarget.19311

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Abstract

Hyo Jeong Yong1, Jeong Su Park2, Ae Lee Jeong1, Sora Han1, Sunyi Lee1, Hye In Ka1, Buyanravjkh Sumiyasuren1, Hyun Jeong Joo1, Su Jeong So1, Ji Young Park1, Do-Young Yoon3, Jong-Seok Lim1, Myeong-Seok Lee1, Hee Gu Lee4 and Young Yang1

1Department of Biological Sciences, Sookmyung Women’s University, Seoul, Republic of Korea

2Department of Severance Biomedical Science Institute, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea

3Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea

4Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea

Correspondence to:

Young Yang, email: [email protected]

Keywords: interleukin-32, von Hippel-Lindau, protein kinase C, hypoxia, apoptosis

Received: March 29, 2017     Accepted: June 12, 2017     Published: July 17, 2017

ABSTRACT

Hypoxia-induced interleukin-32β (IL-32β) shifts the metabolic program to the enhanced glycolytic pathway. In the present study, the underlying mechanism by which hypoxia-induced IL-32β stability is regulated was investigated in ovarian cancer cells. IL-32β expression increased under hypoxic conditions in ovarian cancer cells as it did in breast cancer cells. The amount of IL-32β was regulated by post-translational control rather than by transcriptional activation. Under normoxic conditions, IL-32β was continuously eliminated through ubiquitin-dependent degradation by the von-Hippel Lindau (VHL) E3 ligase complex. Oxygen deficiency or reactive oxygen species (ROS) disrupted the interaction between IL-32β and VHL, leading to the accumulation of the cytokine. The fact that IL-32β is regulated by the energy-consuming ubiquitination system implies that it plays an important role in oxidative stress. We found that IL-32β reduced protein kinase Cδ (PKCδ)-induced apoptosis under oxidative stress. This implies that the hypoxia- and ROS-stabilized IL-32β contributes to sustain survival against PKCδ-induced apoptosis.


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