Research Papers:

Interleukin-32α downregulates the activity of the B-cell CLL/lymphoma 6 protein by inhibiting protein kinase Cε-dependent SUMO-2 modification

Yun Sun Park _, Jeong-Woo Kang, Dong Hun Lee, Man Sub Kim, Yesol Bak, Young Yang, Hee Gu Lee, JinTae Hong and Do-Young Yoon

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Oncotarget. 2014; 5:8765-8777. https://doi.org/10.18632/oncotarget.2364

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Yun Sun Park1, Jeong-Woo Kang1, Dong Hun Lee1, Man Sub Kim1, Yesol Bak1, Young Yang2, Hee Gu Lee3, JinTae Hong4, Do-Young Yoon1

1Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, South Korea

2Research Center for Women's Disease, Department of Life Systems, Sookmyung Women's University, Seoul, South Korea

3Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea

4College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, South Korea

Correspondence to:

Do-Young Yoon, e-mail: [email protected]

Keywords: Interleukin 32α, B-cell CLL/lymphoma 6, Small Ubiquitin-like Modifier-2

Received: April 04, 2014     Accepted: August 14, 2014     Published: October 16, 2014

Abbreviations: PMA, phorbol 12-myristate 13-acetate; PKC, protein kinase C; IL-32, interleukin-32; BCL6, B-cell CLL/lymphoma 6; EV, empty vector


A proinflammatory cytokine IL-32 acts as an intracellular mediator. IL-32α interacts with many intracellular molecules, but there are no reports of interaction with a transcriptional repressor BCL6. In this study, we showed that PMA induces an interaction between IL-32α, PKCε, and BCL6, forming a trimer. To identify the mechanism of the interaction, we treated cells with various inhibitors. In HEK293 and THP-1 cell lines, treatment with a pan-PKC inhibitor, PKCε inhibitor, and PKCδ inhibitor decreased BCL6 and IL-32α protein expression. MAPK inhibitors and classical PKC inhibitor did not decrease PMA-induced BCL6 and IL-32α protein expression. Further, the pan-PKC inhibitor and PKCε inhibitor disrupted PMA-induced interaction between IL-32α and BCL6. These data demonstrate that the intracellular interaction between IL-32α and BCL6 is induced by PMA-activated PKCε. PMA induces post-translational modification of BCL6 by conjugation to SUMO-2, while IL-32α inhibits. PKCε inhibition eliminated PMA-induced SUMOylation of BCL6. Inhibition of BCL6 SUMOylation by IL-32α affected the cellular function and activity of the transcriptional repressor BCL6 in THP-1 cells. Thus, we showed that IL-32α is a negative regulator of the transcriptional repressor BCL6. IL-32α inhibits BCL6 SUMOylation by activating PKCε, resulting in the modulation of BCL6 target genes and cellular functions of BCL6.

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