1;Two Faces of Evil: Cancer and Neurodegeneration;3 1.1;Foreword;5 1.2;Acknowledgments;7 1.3;Contents;9 1.4;Contributors;11 1.5;Updating the Mammalian Cell Cycle: The Role of Interphase Cdks in Tissue Homeostasis and Cancer;15 1.5.1;1 Mammalian Cdks and the Classical Cell Cycle Model;17 1.5.2;2 Interphase Cdks are Not Essential for the Mammalian Cell Cycle;19 1.5.3;3 Limited Compensatory Activities Among Interphase Cdks;21 1.5.4;4 Interphase Cdks Have Evolved to Drive Proliferation of Highly Specialized Cells;24 1.5.5;5 Cell Cycle Cdks and Cancer;25 1.5.6;6 Are Interphase Cdks Required for Tumor Development?;26 1.5.7;References;29 1.6;The Role of Cdk5 as a Cell Cycle Suppressor in Post-mitotic Neurons;31 1.6.1;1 Introduction;32 1.6.2;2 Cdk5 Plays an Important Role in Neuronal Development;32 1.6.3;3 Cdk5 Serves Important Functions in the Regulation of Synaptic Function;33 1.6.4;4 Cdk5 is a Cell Cycle Suppressor in Post-mitotic Neurons;33 1.6.5;5 Cdk5 Inhibits the Cell Cycle in a Kinase-Independent Fashion;34 1.6.6;6 Cdk5 Inhibits the Cell Cycle by Sequestering E2F1;35 1.6.7;7 The Implications of the Central Role of Cdk5 in Neuronal Cell Cycle Suppression;36 1.6.8;References;38 1.7;Actin-SRF Signaling in the Developing and Mature Murine Brain;40 1.7.1;1 Principles of Actin-SRF Signaling in Brain Cells;40 1.7.1.1;1.1 Actin Dynamics Regulates Gene Expression Upon Activation of MRTF-SRF Signaling;40 1.7.1.2;1.2 Actin Dynamics in Neuronal Network Assembly;41 1.7.1.3;1.3 Actin-MRTF-SRF interplay in Neuronal Signaling;42 1.7.2;2 Essential functions of SRF and MRTF in Mouse Brain Development;43 1.7.2.1;2.1 Embryonic Neuronal Migration;43 1.7.2.2;2.2 Axonal Outgrowth, Guidance, and Synaptic Targeting;44 1.7.3;3 Functional Actin-SRF Interplay in the Mature Brain;45 1.7.3.1;3.1 Activity-Induced Gene Expression;45 1.7.3.2;3.2 Learning and Memory;45 1.7.4;4 Linking SRF to Neurodegenerative Diseases, Psychiatric Disorders, and Addiction;46 1.7.4.1;4.1 SRF Protects Against Axonal De-myelination and Degeneration;46 1.7.4.2;4.2 SRF and Epileptic Seizure-Induced Neuronal IEG Expression;47 1.7.4.3;4.3 SRF in M. Alzheimer;47 1.7.4.4;4.4 SRF as a Novel Player in Addictive Behavior and Hyperactive Disorder;48 1.7.5;References;49 1.8;The E3 Ubiquitin Ligase Ube3A Regulates Synaptic Function Through the Ubiquitination of Arc;53 1.8.1;1 A Role for Ube3A in Human Disorders of Cognitive Function;54 1.8.2;2 Ube3a is a Neuronal Activity-Regulated Gene;56 1.8.3;3 Regulation of Synaptic AMPA Receptor Function by Ube3A;57 1.8.4;4 A Novel Proteomic Approach to Ube3A Substrate Identification;60 1.8.5;5 Arc is a Neuronal Ube3A Substrate that Mediates the Effect of Ube3A on AMPAR Trafficking;62 1.8.6;6 Discussion;64 1.8.7;References;66 1.9;Targeting Children´s Brain Tumors: Development of Hedgehog Pathway Inhibitors for Medulloblastoma;69 1.9.1;1 Introduction;69 1.9.2;2 Role of the Hh Pathway in Medulloblastoma;71 1.9.3;3 Targeting Smoothened;72 1.9.4;4 Hh Pathway is Downregulated in Tumor Cell Lines;73 1.9.5;5 Direct Allografts Retain Hh Pathway Activity;74 1.9.6;6 Testing Targeted Therapies in Mice;75 1.9.7;7 HhAntag Eradicates Large Tumors in PtchI+/-p53-/- Mice;75 1.9.8;8 Hh Pathway Inhibition Causes Bone Defects in Young Mice;77 1.9.9;9 Inhibiting the Hh Pathway in the Clinic;79 1.9.10;References;80 1.10;Primary Cilia as Switches in Brain Development and Cancer;84 1.10.1;1 Introduction;84 1.10.2;2 Ciliogenesis;85 1.10.3;3 Primary cilia and Hh signaling;86 1.10.4;4 Primary Cilia in the Specification of Neural Progenitors;88 1.10.5;5 Primary Cilia and Tumorigenesis;89 1.10.6;6 Conclusion;90 1.10.7;References;91 1.11;Nervous System Aging, Degeneration, and the p53 Family;94 1.11.1;1 Introduction;94 1.11.2;2 The p53 Family Regulates Neuronal Survival and Longevity;96 1.11.3;3 p73 Regulates Neurodegeneration;97 1.11.4;4 The p53 Family Regulates Aging in Part by Regulating Adult Stem Cell Pools;99 1.11.5;5 The p53 Family and Neural Precursor Cells;100 1.11.6;6 A M