title: Interleukin-32α downregulates the activity of the B-cell CLL/lymphoma 6 protein by inhibiting protein kinase Cε-dependent SUMO-2 modification.
abstract: 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.
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, South Korea.
authors.forename: Yun Sun
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, South Korea.
authors.forename: Jeong-Woo
authors.initials: JW
authors.lastname: Kang
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, South Korea.
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, South Korea.
authors.forename: Man Sub
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, South Korea.
authors.forename: Yesol
authors.initials: Y
authors.lastname: Bak
authors.affiliation: Research Center for Women's Disease, Department of Life Systems, Sookmyung Women's University, Seoul, South Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
authors.forename: Hee Gu
authors.initials: HG
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, South Korea.
authors.forename: JinTae
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, South Korea.
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
mesh_terms: D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007938:Leukemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051560:Proto-Oncogene Proteins c-bcl-6; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; C496971:IL32 protein, human; D007378:Interleukins; D047428:Protein Kinase Inhibitors; D051560:Proto-Oncogene Proteins c-bcl-6; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; C497255:PRKCE protein, human; D051744:Protein Kinase C-epsilon; D013755:Tetradecanoylphorbol Acetate