title: Inhibition of JNK2 and JNK3 by JNK inhibitor IX induces prometaphase arrest-dependent apoptotic cell death in human Jurkat T cells.
abstract: Exposure of human Jurkat T cells to JNK inhibitor IX (JNKi), targeting JNK2 and JNK3, caused apoptotic DNA fragmentation along with G2/M arrest, phosphorylation of Bcl-2, Mcl-1, and Bim, Δψm loss, and activation of Bak and caspase cascade. These JNKi-induced apoptotic events were abrogated by Bcl-2 overexpression, whereas G2/M arrest, cyclin B1 up-regulation, Cdk1 activation, and phosphorylation of Bcl-2 family proteins were sustained. In the concomitant presence of the G1/S blocking agent aphidicolin and JNKi, the cells underwent G1/S arrest and failed to induce all apoptotic events. The JNKi-induced phosphorylation of Bcl-2 family proteins and mitochondrial apoptotic events were suppressed by the Cdk1 inhibitor. Immunofluorescence microscopic analysis revealed that mitotic spindle defect and prometaphase arrest were the underlying factors for the G2/M arrest. These results demonstrate that JNKi-induced mitochondrial apoptosis was caused by microtubule damage-mediated prometaphase arrest, prolonged Cdk1 activation, and phosphorylation of Bcl-2 family proteins in Jurkat T cells.
authors.affiliation: Laboratory of Immunobiology, School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Won Young
authors.initials: WY
authors.lastname: Jang
authors.affiliation: Laboratory of Immunobiology, School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Laboratory of Immunobiology, School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Seung Tae
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Institute of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Do Youn
authors.initials: do Y
authors.lastname: Jun
authors.affiliation: Laboratory of Immunobiology, School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: ykim@knu.ac.kr.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D016590:Aphidicolin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D048057:Mitogen-Activated Protein Kinase 10 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D049468:Prometaphase / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D016590:Aphidicolin; D048057:Mitogen-Activated Protein Kinase 10; D048056:Mitogen-Activated Protein Kinase 9
keywords: Cdk1 activation; JNK inhibitor IX; Mitochondrial apoptosis; Phosphorylation of Bcl-2 family proteins; Prometaphase arrest