title: 14-3-3 proteins as signaling integration points for cell cycle control and apoptosis.
abstract: 14-3-3 proteins play critical roles in the regulation of cell fate through phospho-dependent binding to a large number of intracellular proteins that are targeted by various classes of protein kinases. 14-3-3 proteins play particularly important roles in coordinating progression of cells through the cell cycle, regulating their response to DNA damage, and influencing life-death decisions following internal injury or external cytokine-mediated cues. This review focuses on 14-3-3-dependent pathways that control cell cycle arrest and recovery, and the influence of 14-3-3 on the apoptotic machinery at multiple levels of regulation. Recognition of 14-3-3 proteins as signaling integrators that connect protein kinase signaling pathways to resulting cellular phenotypes, and their exquisite control through feedforward and feedback loops, identifies new drug targets for human disease, and highlights the emerging importance of using systems-based approaches to understand signal transduction events at the network biology level.
authors.affiliation: Department of Biology, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute for Technology, Cambridge, MA 02139, USA. gardino@mit.edu
authors.forename: Alexandra K
authors.initials: AK
authors.lastname: Gardino
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yaffe
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D008938:Mitosis; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048948:14-3-3 Proteins; D011494:Protein Kinases