title: Heavy metals induce phosphorylation of the Bcl-2 protein by Jun N-terminal kinase.
abstract: The Bcl-2 protein is one of the key components of biochemical pathways controlling programmed cell death. The function of this protein can be regulated by posttranslational modifications. Phosphorylation of Bcl-2 has been considered to be significantly associated with cell cycle arrest in the G2/M phase of the cell cycle, and with cell death caused by defects of microtubule dynamics. This study shows that phosphorylation of Bcl-2 can be induced by heavy metals due to activation of the Jun N-terminal kinase pathway that is not linked to the G2/M cell cycle arrest. Furthermore, we demonstrate that hyperphosphorylated Bcl-2 protein is a more potent inhibitor of zinc-induced cell death than its hypophosphorylated mutant form. These data suggest that regulation of Bcl-2 protein function by phosphorylation is an important part of cell responses to stress.
authors.affiliation: Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlárská 2, CZ-611 37 Brno, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Ondrousková
authors.forename: Jana
authors.initials: J
authors.lastname: Slovácková
authors.forename: Vendula
authors.initials: V
authors.lastname: Pelková
authors.forename: Jirina
authors.initials: J
authors.lastname: Procházková
authors.forename: Karel
authors.initials: K
authors.lastname: Soucek
authors.forename: Petr
authors.initials: P
authors.lastname: Benes
authors.forename: Jan
authors.initials: J
authors.lastname: Smarda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004586:Electrophoresis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019216:Metals, Heavy / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology
chemical_list: D019216:Metals, Heavy; D019253:Proto-Oncogene Proteins c-bcl-2; D048031:JNK Mitogen-Activated Protein Kinases; D015032:Zinc