title: Activation of cyclin E-dependent kinase by DNA-damage signals during apoptosis.
abstract: Preexposure of HL-60 cells to a DNA-damaging agent, cytosine arabinoside (Ara-C), dramatically induced the levels of H1 kinase activities associated with cyclin E (CycE-H1K) but not cyclin A. This induction was cell cycle-independent and accompanied by loss of cell viability, a late event in apoptosis. When an Ara-C-resistant variant of HL-60 cells were treated with Ara-C at a low concentration, neither CycE-H1K nor apoptosis were observed. Both events were induced in the resistant cells but only after treatment with Ara-C at a much higher concentration for a longer period. The DNA-damage-induced CycE-H1K is proposed to be involved in a late apoptosis checkpoint.
authors.affiliation: Department of Pharmacology, University of Pittsburgh School of Medicine, PA, USA.
authors.forename: Q P
authors.initials: QP
authors.lastname: Dou
authors.forename: B
authors.initials: B
authors.lastname: An
authors.forename: C
authors.initials: C
authors.lastname: Yu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019927:Cyclin E; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D003561:Cytarabine / Q000494:pharmacology*; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D006656:Protamine Kinase / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D019927:Cyclin E; D016213:Cyclins; D003561:Cytarabine; D006656:Protamine Kinase; D018844:Cyclin-Dependent Kinases