A significant part of the genome consists of genes that encode proteins with the ability to catalyze the transfer of phosphate to protein substrates thereby altering their biological properties and function. This knowledge has generated considerable interest in the study of these molecules (i.e., protein kinases) in health and their altered function in disease. Indeed, a major current endeavor is to attempt to identify how the functions of protein kinases are altered in disease, and pursuant to that also to find means of targeting these enzymes to alter their expression or function for therapeutic interventions. In this context, protein kinase CK2 has emerged as an important player by virtue of its various unique characteristics in cell function. CK2 (adopted acronym for the former inappropriate name casein kinase II) is a protein serine/threonine kinase that is among the most highly conserved molecules, and is present in every cell at a strictly regulated level depending on the cell type. It appears that moderate upregulation of the enzyme level provokes enhanced oncogenic potential in cells, whereas downregulation of the enzyme promotes cell death. Thus, CK2 plays key roles in cellular growth and survival. The observation that CK2 was elevated (at the level of protein) in various cancers that have been examined pointed to its involvement in the cancer phenotype. A role for CK2 in oncogenesis was further strengthened by recognition of its ability to act as a potent suppressor of apoptosis besides its function in cell proliferation. Accordingly, during recent years efforts have been directed toward generating strategies to target CK2 for cancer therapy. In addition, new roles for CK2 in diverse biological processes are beginning to be recognized as is noted in some of the contributions to these Proceedings of the Fifth International Conference on CK2.
For a number of years, scientists interested in the subject of CK2 have gathered every three years to discuss the progress in various aspects of CK2 properties and functions. The four previous meetings were held in Heidelberg, Germany (1994), Villard de Lans, France (1997), San Esteban, Chile (2000), and London, Ontario, Canada (2004). The 5th International Conference on protein kinase CK2 was held 13–16 September 2007 in the historic city of Padua (Padova), Italy, at the Venetian Institute of Molecular Medicine (VIMM) and University of Padua. The theme of this meeting (also recognized as a symposium of the International Union of Biochemistry & Molecular Biology) was “Protein Kinase CK2 in Health and Disease” which was most befitting considering that the meeting was held in Padua, seat of the oldest medical school in the world. The meeting was attended by several investigators who discussed recent developments in the field of CK2.
Prior to the start of the regular meeting program, the participants were treated to an enjoyable and highly informative lecture entitled “The Origin of Modern Medicine at the University of Padua during Renaissance” which was delivered by Professor Gaetano Thiene of the Department of Pathological Anatomy, University of Padua. This lecture, though not part of the formal program of the CK2 meeting, highlighted important historical developments in the region that led to active medical inquiry at a very early stage and was eventually important in the development of modern medical science. The meeting was formally opened by Lorenzo A. Pinna (Padua, Italy) who described the general plan of the meeting noting that the contents of the meeting would include diverse areas dealing with CK2 function reflecting an expanding interest in the biology of CK2. The following is a brief outline of the content of various talks presented in this meeting.
Session I entitled “Regulatory devices and structure-function analysis” consisted of five talks. The first talk was by David Litchfield (London, Canada) who presented studies describing modes of regulation of CK2 by protein interactions. The second talk was by Karsten Niefind (Cologne, Germany) who highlighted structural features of CK2 and its subunits based on elegant crystal structure studies of the enzyme in the presence of ligands. The third talk was by Jorge Allende (Santiago, Chile) who described studies on the role of the β subunit in promoting translocation of CK2 holoenzyme to the outer surface of the cell membrane, as well as studies on activity of chimeric protein kinase CK2α/CK1 constructs. Brigitte Olsen (Odense, Denmark) then presented recent efforts to identify structural differences in CK2 subunits and holoenzyme constructs. The final talk in this session was by Miwako Homma (Fukushima, Japan) who described studies on cell cycle-related nuclear translocation of CK2 and the role of CK2 in cell cycle-related phosphorylation of certain key substrates.
Session II was devoted to “Pharmacological Down-Regulation of CK2.” This session was started by a general talk by Doriano Fabbro of Novartis (Basel, Switzerland) describing his general experience relating to issues and successes in development of agents suitable for clinical targeting of protein kinases. This was followed by a talk by Roberto Battistutta (Padua, Italy) who presented studies on investigation of inhibitors of CK2 exploiting the structural features of the kinase. Claude Cochet continued this theme discussing studies on high throughput approaches to generate new chemical inhibitors of CK2 that bind to the enzyme by different modes, and on a class of inhibitors that promote disruption of the subunit interaction in CK2 resulting in enzyme inhibition. The session ended with a talk by Maria Bretner (Warszawa, Poland) who highlighted synthesis of derivatives of tetrabromobenzotriazole and tetrabromobenzimidazole, and their pharmacokinetic studies in rats.
The first talk in Session III entitled “CK2 and cell fate (implications in apoptosis, differentiation, survival, etc.)” was by Khalil Ahmed (Minneapolis, USA) who gave an overview of studies on the role of CK2 in apoptosis and its impact on various downstream targets in the apoptotic machinery. David Meek (Dundee, Scotland) discussed studies dealing with the involvement of TAFII250 and CK2 in phosphorylation of the acidic domain of Mdm2. Odile Filhol touched on interesting novel aspects of CK2 function, namely its potential role in epithelial to mesenchymal transition, and in cell polarity. Barbara Guerra (Odense, Denmark) presented data on interaction of CK2 subunits with other kinases during cell cycle progression highlighting regulatory features resulting from these interactions. Yoshiko Miyata (Kyoto, Japan) presented data on the analysis of Cdc37 phosphorylation on serine 13 by employing a specific anti-pSerine13-Cdc37 antibody, suggesting the potential of this antibody to serve as a tool to evaluate in vivo CK2 activity. In describing a novel function of CK2, Said Hashemolhosseini (Erlangen, Germany) presented investigations indicating the essential role of CK2 in maintaining motor end plates, and the application of these studies to muscle pathologies. David Seldin (Boston, USA) gave a review of his studies on the roles of the two catalytic subunits of CK2 in mouse development, and highlighted the role of CK2α in mouse embryogenesis.
Session IV was devoted to “Implications of CK2 in cancer and other diseases.” In this session, Khalil Ahmed (Minneapolis, USA) discussed strategies for therapeutic targeting of CK2 for cancer therapy, focusing on induction of apoptosis employing cell culture and orthotopic prostate cancer models mediated by antisense CK2αα′ or siRNA delivered as naked molecules or in a nanocapsule. Pier Paolo Scaglioni (Dallas, USA) presented studies on the role of CK2-mediated phosphorylation in degradation of the PML tumor suppressor through ubiquitin mediated degradation. Maria Ruzzene (Padua, Italy) highlighted studies on expression of CK2 in diverse cancer cells relating to their relative drug resistance, and the effect of manipulating CK2 levels on the multi-drug resistant phenotypes. Silvio Perea (Havana, Cuba) described studies on a novel CIGB-300 proapoptotic peptide that impairs CK2-mediated phosphorylation to examine its anti-tumor properties in cancer animal models and in human cervical cancer patients, representing a first attempt to target CK2 function in a clinical setting. Pursuing the role of CK2 in other disease processes, Anil Mehta (Dundee, Scotland) gave an overview of his pioneering studies on the role of CK2 in cystic fibrosis, while Alexander Ljubimov (Los Angeles, USA) gave a detailed account of their ongoing original studies on the role of CK2 in retinal angiogenesis.
The final session (V) was devoted to studies dealing with “New targets and interacting partners of CK2”. Thierry Buchou (Grenoble, France) presented a talk on genetic links of CK2β with bHLH transcription factor. The final talk was by Mathias Montenarh (Homburg, Germany) who detailed studies which have identified novel binding partners of CK2α and CK2α′ subunits, such as certain spliceosome factors. These data suggested distinct roles of the two catalytic subunits of CK2 in the splicing process.
The meeting ended with the recognition that the CK2 field had expanded significantly during the past three years since the previous meeting. The various talks presented at the meeting indicate the emerging importance of CK2 in diverse functions in health and disease. This Focused Issue of Molecular and Cellular Biochemistry presents 22 articles describing most of the conference presentations and highlighting the latest progress on CK2 research. We express our sincere thanks to the participants of the meeting and contributors of these papers. In addition to these formal presentations at the meeting, additional studies were also described in Poster Sessions which involved young investigators.
The international organizing committee of the CK2 conferences consists of Khalil Ahmed (USA), Jorge Allende (Chile), Claude Cochet (France), Olaf-Georg Issinger (Denmark), David Litchfield (Canada), Lorenzo A. Pinna (Italy), and Walter A. Pyerin (Germany). However, the major credit for the organization of the conference (in Padua, Italy) goes to the local organizers Lorenzo A. Pinna and Flavio Meggio, who were assisted by Monica Vettore (for administrative support) and by several collaborators, most notably Oriano Marin, Luca Cesaro, Andrea Venerando, and Elena Papinutto. Guixia Wang and Janeen Trembley (Minneapolis) provided excellent editorial assistance during the compilation of these Proceedings. Generous support for the meeting was provided by the International Union of Biochemistry & Molecular Biology, The University of Padua, Venetian Institute of Molecular Medicine, European Union Consortium “Protein Kinases—Novel Drug Targets of Post Genomic Era,” Associazione per lo Studio dei Tumori e dell Malattie Polmonari, and Applied Biosystems. The organizers and participants are deeply appreciative of their support as it was critical for making it possible to convene the Fifth International Meeting on CK2.
Guest editor: Khalil Ahmed, Minneapolis, USA
Guest co-editors: Olaf-Georg Issinger, Odense, Denmark
Flavio Meggio, Padua, Italy
Lorenzo A. Pinna, Padua, Italy