Histone H1 dephosphorylation is mediated through a radiation-induced signal transduction pathway dependent on ATM.
Ionizing radiation is known to activate multiple signal transduction pathways, but the targets of these pathways are poorly understood. Phosphorylation of histone H1 is thought to have a role in chromatin condensation/decondensation, and we asked whether ionizing radiation (IR) would alter H1 phosphorylation. Our data demonstrate that low doses of IR result in a dramatic, but transient, dephosphorylation of H1 isoforms. The in vivo IR-induced dephosphorylation of H1 is completely blocked by wortmannin and is abrogated in ataxia telangiectasia cells. Furthermore, we measured radiation-induced inhibition of cyclin dependent kinase activity and activation of histone H1 phosphatase activity. Both activities were affected by radiation-induced signals in an ATM-dependent manner. Thus, the rapid IR-induced dephosphorylation of H1 involves a pathway including ATM and a wortmannin-sensitive step leading to both inhibition of cyclin-dependent kinase activities as well as activation of H1 phosphatase(s).
Guo
C Y
CY
Department of Radiation Oncology, University of Virginia Health Science System, Charlottesville, Virginia 22908, USA.
Wang
Y
Y
Brautigan
D L
DL
Larner
J M
JM
D000730:Androstadienes / Q000494:pharmacology; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004249:DNA Damage; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D016350:Leucine Zippers; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D000077191:Wortmannin
D000730:Androstadienes; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006657:Histones; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D025521:Tumor Suppressor Proteins; D000077191:Wortmannin; C576324:ATM protein, human