title: Cell apoptosis: requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3.
abstract: Immunofluorescence studies have revealed that H2AX is phosphorylated at the sites of DNA double-strand breaks induced by ionizing radiation and is required for recruitment of repair factors into nuclear foci after DNA damage. Therefore, the function of H2AX is believed to be associated primarily with repair of DNA damage. Here, we report a function of H2AX in cellular apoptosis. Our data showed that H2AX is phosphorylated by UVA-activated JNK. We also provided evidence showing that UVA induces caspase-3 and caspase-activated DNase (CAD) activity in both H2AX wild-type and H2AX knockout mouse embryonic fibroblasts (MEFs). However, DNA fragmentation occurred only in H2AX wild-type MEFs. Furthermore, H2AX phosphorylation was critical for DNA degradation triggered by CAD in vitro. Taken together, these data indicated that H2AX phosphorylation is required for DNA ladder formation, but not for the activation of caspase-3; and the JNK/H2AX pathway cooperates with the caspase-3/CAD pathway resulting in cellular apoptosis.
authors.affiliation: Hormel Institute, University of Minnesota, Austin, 55912, USA.
authors.forename: Chengrong
authors.initials: C
authors.lastname: Lu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Yong-Yeon
authors.initials: YY
authors.lastname: Cho
authors.forename: Faqing
authors.initials: F
authors.lastname: Tang
authors.forename: Tatyana
authors.initials: T
authors.lastname: Zykova
authors.forename: Wei-ya
authors.initials: WY
authors.lastname: Ma
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D004789:Enzyme Activation; D006657:Histones / Q000494:pharmacology / Q000502:physiology / Q000528:radiation effects*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction; D014162:Transfection; D014466:Ultraviolet Rays; D015854:Up-Regulation
chemical_list: D053148:Caspase 3; D020169:Caspases; D004247:DNA; D006657:Histones; D048031:JNK Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; C475961:gamma-H2AX protein, mouse