Protein kinase CK2: a catalyst for biology, medicine and structural biochemistry
- 281 Downloads
KeywordsChronic Lymphocytic Leukemia Focus Issue Retinal Progenitor Cell Final Talk Dopamine Receptor Signaling
Protein kinase signaling in the cell is well recognized as a key mechanism through which a whole variety of cellular functions are mediated. Considering that the phosphoproteome constitutes a significant part of the expressed genome, it is not surprising that this mode of signaling is involved in virtually all aspects of normal and abnormal cell activities. In particular, dysregulation of these signals in the cell appears to play a key role in diverse types of disease processes, and to that end, protein kinases have emerged as attractive targets in the generation of therapeutic approaches. In this context, protein kinase CK2 (adopted acronym for the former inappropriate name casein kinase II) has continued to attract the increasing attention for its involvement in diverse cellular activities in both the normal and the disease states.
CK2 is one among the most highly conserved molecules and is present in every cell at an apparently strictly regulated level depending on the cell type. A great deal of current information suggests that the moderate upregulation of the enzyme level provokes enhanced oncogenic potential in cells, whereas its downregulation promotes cell death. Increased levels of CK2 have been observed in various cancers that have been examined and appear to be related to prognosis; thus, it would seem that elevated CK2 plays a dual role in cancer cell phenotype—promotion of cell growth and proliferation as well as potent suppression of apoptosis. The demonstration of the druggability of CK2 has stimulated efforts directed towards generating strategies to target CK2 for cancer therapy. Likewise, new roles for CK2 in diverse biologic processes continue to be recognized. Indeed, based on the current observations in the literature, it is fair to state that CK2 has emerged as a “master regulator” of cell functions. These various developments are highlighted in the contributions to the present Focused Issue of Molecular and Cellular Biochemistry. The articles published in this Focused Issue are selected from the presentations at the Sixth International Conference on CK2. The Sixth International Conference on Protein kinase CK2 was held 7–10 September 2010, at Wahn Castle in the historic city of Cologne, Germany, as “A symposium of the International Union of Biochemistry and Molecular Biology” organized by the Institute of Biochemistry, Department of Chemistry of the University of Cologne. The theme of the Sixth International Conference on CK2 was “Protein kinase CK2—a catalyst for biology, medicine and structural biochemistry”. The meeting was attended by investigators who discussed recent developments in the field of CK2, and had a truly international representation of scientists from 20 different countries and several continents.
The meeting was opened with welcome addresses by Professor Dr. Christiane Bongartz (Dean of Faculty of Arts and Humanities of the University of Cologne), by Professor Dr. Günter Schwarz (Director in Chief of the Institute of Biochemistry, Department of Chemistry, Faculty of Mathematics and Natural Sciences of the University of Cologne), and by Dr. Karsten Niefind (Institute of Biochemistry, local organizer of the CK2 conference). Prior to the start of the regular meeting program, the participants were treated to a truly enjoyable and highly informative Welcome Lecture entitled “The Origins of the Roman Cologne” delivered by Professor Dr. Werner Eck (Faculty of Arts and Humanities, Historical Institute, University of Cologne). The formal program of the meeting was then opened by Karsten Niefind (Cologne, Germany) who described the general organization of the meeting noting the truly international character of the sixth CK2 meeting, and the diverse areas dealing with CK2 function reflecting an ever-expanding interest in the biology of this signal. The following is a brief description of the various talks presented in this meeting.
Session A entitled “CK2 and Cancer” consisted of several talks dealing with the biology of CK2 in cancer cells as well as the development of approaches to target CK2 in cancer cells for therapeutic purposes. The session was opened with a talk by Lorenzo A. Pinna (Padua, Italy) who gave an overview of the implications of CK2 overexpression in cancer as an example of a non-oncogene addiction by these cells. Khalil Ahmed (Minneapolis, USA) described interactions of protein B23 and CK2 in normal and cancer cells in response to diverse growth and apoptotic stimuli. This was followed by a talk by Janeen Trembley (Minneapolis, USA) who described approaches to molecular targeting of CK2 in cancer therapy. Kenna Anderes and Fabrice Pierre (San Diego, USA) presented data on the discovery and properties of a novel orally active inhibitor of CK2 with the potential for treatment of cancer. Odile Filhol (Grenoble, France) presented results on the expression of CK2 subunits in epithelial mesenchymal transition and its clinical implications. Silvio Perea (Havana, Cuba) described studies on a peptide that targets CK2 phosphorylation sites for its application in cancer therapy. The final talk in this session was by Leila R. Martins (Lisboa, Portugal) who described work on therapeutic targeting of CK2 in chronic lymphocytic leukemia.
The theme of Session B was “Structure-based development of selective CK2 inhibitors”. In this session, Roberto Battistutta (Padua, Italy) described new developments in the study of the structural basis of CK2 inhibitors directed to the ATP binding site. Claude Cochet (Grenoble, France) described the inhibitors that act at allosteric sites of CK2. Andreas Gratz (Düsseldorf, Germany) explained a non-radioactive method of measuring CK2 activity as a tool for inhibitor studies. Takayoshi Kinoshita (Osaka, Japan) discussed the application of thermodynamic and computational approaches in the design of CK2 inhibitors. Maria Bretner (Warsaw, Poland) also described the design and the synthesis of novel CK2 inhibitors. Andrily Golub (Kyiv, Ukraine) discussed the search for new compounds that could serve as inhibitors of CK2. Likewise, Maciej Maslyk (Madrid, Spain) presented studies on a new prototype in the design of CK2 inhibitors.
The theme of Session C was “CK2 as a cell survival factor.” In this session, David Meek (Dundee, UK) described studies on the role of CK2 in regulation of the p53 pathway. Birgitte Olsen (Odense, Denmark) discussed studies on the effect of the absence of catalytic subunit of DNA-dependent protein kinases on the expression of CK2α′ in the cell. The subject of Barbara Guerra’s talk (Odense, Denmark) was the interaction of CK2 and catalytic subunits of DNA-PK. In the final talk in this session, Julio Tapia (Santiago, Chile) discussed the involvement of CK2 in the canonical Wnt-signaling pathway through activation of AKT/PKB.
Session D focused on “Impact of CK2 in signal transduction.” In this session, David Litchfield (London, Canada) discussed the convergence of CK2 with caspase signaling pathways in the control of cell survival and proliferation, and Heike Rebholz discussed (New York, USA) the function of CK2α in dopamine receptor signaling. Mathias Montenarh (Homburg, Germany) presented studies on new interacting partners of CK2. Cathleen Juhl (Leipzig, Germany) discussed the role of CK2 in adiponectin signaling. Rossukon Thongwichian (Berlin, Germany) described application of in-cell NMR spectroscopy for comparative analysis of CK2 phosphorylation of multiple adjacent substrates. The final talk in the session by Carolina Dudenhoeffer-Carneiro (Rio de Janeiro, Brazil) focused on CK2 dynamics in the activity of retinal progenitor cells.
Session E was devoted to “CK2 in yeasts, plants, and non-vertebrate animals.” In this session, the first talk was by Carmen Martinez (Barcelona, Spain) who discussed the role of CK2 in plant signal transduction. Grażyna Muszyńska (Warsaw, Poland) gave an overview of the forms and role of CK2 in Zea mays. Kendra Tosoni (Padua, Italy) presented data on the p23 co-chaperone protein as a novel substrate of CK2 in Arabidopsis. Marta Riera (Barcelona, Spain) presented a work on the role of the plant-specific N-terminal domain of maize CK2β1 subunit in CK2β functions and holoenzyme regulation. Ryszard Szyszka (Lublin, Poland) presented a discussion on yeast CK2 describing its structure, substrates, and regulation. Paola Coccetti (Milano, Italy) discussed observations on modulation of CK2 by nutritional conditions in budding yeast. Hiroshi Murakami (Nagoya, Japan) described the role of CK2 in cell cycle check points in fission yeast. Sophia Kouyanou-Koutsoukou (Athens, Greece) presented data on cloning and characterization of CK2 subunits of the Mediterranean fly Ceratitis capitata.
Session F was dedicated to “CK2 and nuclear trafficking.” In this session, Yoshiki Tsuchiya (Kyoto, Japan) described studies on the role of CK2 in mammalian circadian rhythm. Yoshihiko Miyata (Kyoto, Japan) presented data on a possible role of CK2 in protein nuclear translocation signaling (NLS) using GRP94 as a model protein. Alexander Plotnikov’s contribution (Rehovot, Israel) suggested the involvement of CK2 in the nuclear translocation of ERK. In the final talk in this session, Sinisa Dovat (Hershey, USA) presented observations on the control by CK2 of Ikaros function in lymphocyte differentiation, chromatin remodeling, and tumor suppression.
Session G was devoted to “CK2 in developmental biology.” In this session, Isabel Dominguez (Boston, USA) described studies on the essential function of CK2α for embryonic morphogenesis. Ashok Bidwai (Morgantown, USA) presented data on the roles of CK2α and CK2α′ subunits during notch-mediated neuronal patterning in Drosophila. David Seldin (Boston, USA) discussed the control of cell proliferation and growth by catalytic subunits CK2α and CK2α′ in vivo. The meeting ended with a final general talk presented by Karsten Niefind (Cologne, Germany) on the structural features that distinguish CK2α and CK2α′. We wish to note that the spine concept pertaining to CK2 catalytic function discussed in the manuscripts by Karsten Niefind and by Roberto Battistutta was developed independently; these articles are published side-by-side in the Proceedings.
At the conclusion of the meeting, there was a general recognition that the CK2 field had continued to expand significantly since the previous meeting held in 2007 at Padua, Italy. The various talks presented at the meeting indicate the emerging importance of CK2 in diverse functions in health and disease. The 33 articles in this Focused Issue of Molecular and Cellular Biochemistry highlight the latest progress in CK2 research. We express our sincere thanks to the contributors to this Focused Issue.
The International Organizing Committee for the sixth CK2 conference consisted of Khalil Ahmed (USA), Maria Bretner (Poland), Claude Cochet (France), Olaf-Georg Issinger (Denmark), David Litchfield (Canada), Karsten Niefind (Germany), and Lorenzo A. Pinna (Italy). However, the major credit for the organization of the conference in Cologne, Germany, goes to the local organizer Karsten Niefind who, with the support of the Institute of Biochemistry and assistance of Michael Zimmermann, Helga Niefind, Elena Brunstein, Nils Bischoff and Christine Tölzer, made all the arrangements for the efficient progress of the meeting. In addition, during the preparation and compilation of these Proceedings, Janeen Trembley (Minneapolis, USA) provided excellent editorial assistance.
The meeting was generously sponsored by the International Union of Biochemistry & Molecular Biology (IUBMB), Fond der Chemischen Industrie (FCI), Deutsche Forschungsgemeinschaft (DFG), University of Cologne, KoelnAlumni—Verein der Freunde und Förderer der Universität zu Köln e.V., and by the companies KinaseDetect ApS (Odense, Denmark), Cylene Pharmaceuticals (San Diego, USA), and Oxford Diffraction (Oxford, UK). The organizers and participants are deeply appreciative of their support which was critical for making it possible to convene the Sixth International Meeting on CK2 in Cologne, Germany.