Protein Kinase CK2

CONTRIBUTORS xi PREFACE xv PART 1 MOLECULAR AND STRUCTURAL ASPECTS 1 1 Structural Bases of Protein Kinase CK2 Function and Inhibition 3 Karsten Niefind and Roberto Battistutta Introduction 3 Basic Structure/Function Relationships of CK2 8 CK2 Inhibitors 37 Conclusions and Outlook 60 Acknowledgments 61 2 The Interactome of Protein Kinase CK2 76 Mathias Montenarh and Claudia Götz Introduction 76 From the Outside to the Inside: Interaction of CK2 with Membrane Proteins 78 Regulating Gene Expression: Interaction of CK2 with Components of Signaling Cascades, Transcription Factors and DNA Modifying Enzymes 82 Mastering Nucleic Acid Functions: Interaction of CK2 with Proteins of the Replication, Transcription, and Translation Machinery of the Cell 87 Let It Roll: Interaction of CK2 with Cell Cycle Regulatory Proteins 90 Guardian Angels: Interaction of CK2 with Proteins That Maintain the Cellular Integrity 93 Live and Let Die: Interaction of CK2 with Proteins of the Apoptotic Pathway 96 Highways in the Cell: Interaction of CK2 with the Cytoskeleton and Motor Proteins 96 Collaborating with the Enemy: Interaction of CK2 with Proteins Implicated in Viral Infections 98 Last But Not Least: Miscellaneous 99 Concluding Remarks 101 3 CK2 Contribution to the Generation of the Human Phosphoproteome 117 Luca Cesaro and Mauro Salvi Kinases Contribution to the Human Phosphoproteome 117 CK2 Substrate Specifi city 118 Subphosphoproteomes of Proteins with Specific Functions 122 Subphosphoproteomes of Cellular Compartments 123 Absolute Quantification of Yeast Phosphoproteome Reflects the Constitutive Activity of CK2 125 Conclusions 125 Acknowledgments 126 PART 2 FUNCTIONAL ASPECTS 129 4 CK2 in Embryonic Development 131 Laura Macias Alvarez, Jesus Revuelta-Cervantes, and Isabel Dominguez CK2 in Yeast Biology 131 CK2 in Invertebrate Development 135 CK2 in Vertebrate Development 139 CK2 in Plant Development 148 CK2 in Animal Developmental Signaling Pathways 149 Discussion 155 Outlook 157 Acknowledgments 158 5 Protein Kinase CK2: At the Crossroads of Pathways Controlling Cell Proliferation and Survival 169 Michelle Gabriel and David W. Litchfield General Introduction 169 Protein Kinase CK2 170 CK2 in Cancer 171 Involvement of CK2 in Signaling Pathways Controlling Proliferation and Death 172 Concluding Remarks 182 Acknowledgments 183 6 The Role of Protein Kinase CK2 in the p53 Response 190 David W. Meek Protein Kinase CK2 190 The p53 Network 191 The Interaction Between p53 and CK2 192 Regulation of p53 by Phosphorylation of Ser392 193 Proposed Mechanism for Regulation of p53 Phosphorylation at Ser392 (the “CK2” Site) 194 Phosphorylation of p53 by CK2 in a Physiological Context? 196 A Broader Role for CK2 in Regulating the p53 Network? 197 7 The Pivotal Role of CK2 in the Kinome-Targeting Hsp90 Chaperone Machin