Protein Kinase CK2 Cellular Function in Normal and Disease States

The field of protein kinases has greatly impacted our understanding of the basic mechanisms in cell function. The field has also been a major focus of drug development that considers the broad reach of the protein kinase function under diverse conditions. One member of the kinome, protein kinase CK2, continues to emerge as a major signaling molecule involved in diverse functions in health and disease. This kinase has unique features, most notably its ubiquitous and highly conserved nature. Its vast number of potential substrates exemplifies its involvement in various functions in cells under both the normal and diseased states. Of particular note is the observation that due to its ubiquitous nature, CK2 has been found to be dysregulated in all cancers that have been examined. As such, it is now being considered a potentially important target for cancer therapy.

Protein Kinase CK2 plays equally important functions in development and intracellular activities, and has a global impact on cell growth and proliferation. An additional key function of CK2 is the impact of its activity on cell death processes. Given the vast nature of its functions, CK2 has been proposed to serve as a "master regulator" of cell function. The chapters included in this work cover a wide range of topics dealing with some of the functions mentioned above, providing an important starting point for research investigators and graduate students interested in this field.

Auteur

Dr. Khalil Ahmed is a Professor at the University of Minnesota, and a Senior Research Career Scientist at Minneapolis VA Health Care System, Minneapolis, Minnesota, U.S.A. He has a long history of studies on the functional biology of protein kinase CK2 in normal and neoplastic cells. He originally described the signal mediated dynamic shuttling of CK2 in the cell, and discovered the role of CK2 as a suppressor of apoptosis. His current research is focused on the mechanism of CK2 regulation of cell death. He is also studying the development of molecular therapeutic strategies using a nanomedicine approach for treatment of prostate and other cancers.

Dr. Olaf-Georg Issinger is a Professor at the University of Southern Denmark, Odense, Denmark. He has been involved in the initial cloning and characterization of protein kinase CK2, a prerequisite for the elucidation of its structure in the absence and presence of specific interaction molecules. His current research focuses on the exploration of cellular signaling pathways in cell lines with respect to the role of various protein kinases using newly characterized kinase inhibitors identified by screening small chemical compound libraries.

Dr. Ryszard Szyszka is a Professor at the John Paul II Catholic University of Lublin, Poland. He is head of the Department of Molecular Biology and Dean of the Faculty of Biotechnology and Environmental Sciences. His research is focused on the identification and characterization of new substrates of protein kinase CK2 from Saccharomyces cerevisiae. Further areas of interest include the structure and regulation of yeast CK2, and discovery of novel CK2 inhibitors.

Résumé
Protein kinase CK2 (formerly casein kinase II or 2) is known to play a critical role in the control of cell growth and cell death and is thus intimately involved in the development of cancer. More specifically, CK2 has been found to be elevated in all cancers examined. While CK2 levels are known to be high in proliferating normal cells, CK2 has also been found to be a potent suppressor of apoptosis and is a link to the cancer cell phenotype, which is characterized by deregulation of both cell proliferation and cell death. Indeed, it would appear that CK2 impacts many of the hallmarks of cancer and it has now gained considerable attention as a potential target for cancer therapy. Protein Kinase CK2 and Cellular Function in Normal and Disease States increases knowledge of the role of CK2 in the development of cellular dysfunction and emphasizes that this protein may serve as a target of drug development for improved cancer therapy. In addition, it is a handy tool that provides cancer researchers, graduate students, and all scientists involved in CK2 research with one main source for the latest advances in CK2 research.

Contenu

1. CK2 Suppression of Apoptosis.- 2. Structural Determinants of CK2 Regulation.- 3. Targeting Protein Kinase: CK2 Suppresses Pro-Survival Signaling Pathways and Growth of Gliobastoma.- 4. The Roles of CK2 in Drosophila Neurogenesis.- 5. Targeting the CK2 Subunit Interface: Challenge and Usefulness.- 6. CK2 in Wnt/ß-catenin signaling and embryo development.- 7. Defective expression of CK2ß promotes EMT and stemness properties both required for breast cancer progression.- 8. Chemical Biology Approaches to Identify CK2 Substrates and Perform Unbiased Evaluation of CK2 Inhibitors.- 9. Development of Screening Systems and Identification of Novel Potent Inhibitors of Human Protein Kinase CK2.- 10. Protein Kinase CK2: At the Crossroad of Regulatory Cellular Pathways.- 11. Functional Regulation of DYRK Family Protein Kinases by Cellular Binding Partners.- 12. Regulation of CK2 in pancreatic ß cells.- 13. Recent impressions from the configurational and conformational space captured by protein kinase CK2.- 14. Role of CK2 in Plant Responses to Abiotic Stress.- 15. "Genuine" Casein Kinase: The False Sister of CK2: Phosphorylates-Secreted Proteins.- 16. CK2: - A Novel Player in L-DOPA induced dyskinesia in a mouse model of Parkinson's disease.- 17. CK2 function in the regulation of Akt Pathway: new findings and perspectives.- 18. CK2 structure from yeast to human.- 19. Cellular zinc signaling is triggered by CK2.- 20. A Nanomedicine Approach to Targeting CK2 for Cancer therapy.- 21. Bisubstrate approach for construction of high-affinity inhibitors and optical probes for protein kinase CK2.