title: Defective anchoring of JNK1 in the cytoplasm by MKK7 in Jurkat cells is associated with resistance to Fas-mediated apoptosis.
abstract: The c-Jun N-terminal protein kinase (JNK) plays a context-dependent role in tumorigenesis. Stress-induced redistribution of JNK from the cytoplasm to the nucleus has been demonstrated as essential for stress-induced cell death. However, accumulation of basal JNK activity in the nucleus has frequently been seen in tumor cells. Our previous report revealed aberrant nuclear entry of JNK protein in Jurkat human leukemic T-cells even without JNK hyperactivation. Because inhibition of JNK activity, especially JNK1 activity, in Jurkat cells results in augmented Fas-mediated apoptosis, it is possible that aberrant subcellular localization of JNK, especially the JNK1 isoform, contributes to the resistance to Fas-mediated apoptosis. Here we report that MKK7 works as a cytoplasmic anchoring protein for JNK1 in various types of cells, including human peripheral blood mononuclear cell (PBMC) T-cells, but exhibits aberrant nuclear entry in Jurkat cells. Ectopic expression of a JNK1 mutant defective of nuclear entry or a nuclear JNK inhibitor leads to impaired UV-induced apoptosis in both PBMC T- and Jurkat cells. The same treatment shows no effect on Fas-mediated apoptosis of PBMC T-cells but sensitizes Jurkat cells to Fas-mediated apoptosis. Taken together, our work suggests that aberrant subcellular organization of the JNK pathway might render certain tumor cells resistant to Fas-mediated apoptosis.
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Ruihong
authors.initials: R
authors.lastname: Tang
authors.forename: Ming
authors.initials: M
authors.lastname: Lv
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Wang
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Guo
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.forename: Chunxia
authors.initials: C
authors.lastname: Qiao
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.forename: Xinying
authors.initials: X
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.forename: Jiyan
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D003593:Cytoplasm / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D048688:MAP Kinase Kinase 7 / Q000378:metabolism*; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D015398:Signal Transduction; D013347:Subcellular Fractions; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D019014:fas Receptor; D048055:Mitogen-Activated Protein Kinase 8; D048688:MAP Kinase Kinase 7; C482569:MAP2K7 protein, human