Related Experiment Video
Updated: Mar 8, 2026
Combining Computer Game-Based Behavioural Experiments With High-Density EEG and Infrared Gaze Tracking
Published on: December 16, 2010
Exploring the CK2 Paradox: Restless, Dangerous, Dispensable
Cinzia Franchin1,2, Christian Borgo3, Silvia Zaramella4
1Department of Biomedical Sciences, University of Padova, via U. Bassi, 58/B, 35131 Padova, Italy. cinzia.franchin@unipd.it.
Abstract:
The history of protein kinase CK2 is crowded with paradoxes and unanticipated findings. Named after a protein (casein) that is not among its physiological substrates, CK2 remained in search of its targets for more than two decades after its discovery in 1954, but it later came to be one of the most pleiotropic protein kinases. Being active in the absence of phosphorylation and/or specific stimuli, it looks unsuitable to participate in signaling cascades, but its "lateral" implication in a variety of signaling pathways is now soundly documented. At variance with many "onco-kinases", CK2 is constitutively active, and no oncogenic CK2 mutant is known; still high CK2 activity correlates to neoplasia. Its pleiotropy and essential role may cast doubts on the actual "druggability" of CK2; however, a CK2 inhibitor is now in Phase II clinical trials for the treatment of cancer, and cell clones viable in the absence of CK2 are providing information about the mechanism by which cancer becomes addicted to high CK2 levels. A phosphoproteomics analysis of these CK2 null cells suggests that CK2 pleiotropy may be less pronounced than expected and supports the idea that the phosphoproteome generated by this kinase is flexible and not rigidly pre-determined.
Insights
Protein kinase CK2 (casein kinase 2) is paradoxically linked to cancer despite its constitutive activity. New research on CK2-null cells reveals its phosphoproteome is flexible, not predetermined.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Protein kinase CK2 (CK2) has a complex history, initially misnamed and later found to be highly pleiotropic.
- Despite constitutive activity and no known oncogenic mutants, high CK2 levels correlate with cancer development.
- CK2's essential role and pleiotropy raise questions about its 'druggability' as a cancer target.
Purpose of the Study:
- To investigate the role of CK2 in cellular signaling and its connection to cancer.
- To explore the phosphoproteome landscape in the absence of CK2 activity.
- To understand how cancer cells become dependent on high CK2 levels.
Main Methods:
- Review of historical findings and current research on CK2.
- Analysis of phosphoproteomics data from CK2-null cells.
- Clinical trial updates on CK2 inhibitors for cancer treatment.
Main Results:
- CK2's involvement in signaling pathways is well-documented, despite its unusual activity profile.
- A CK2 inhibitor is currently in Phase II clinical trials for cancer therapy.
- Phosphoproteomics analysis of CK2-null cells suggests CK2's pleiotropy might be less extensive than previously thought.
- The phosphoproteome regulated by CK2 appears flexible and not rigidly predetermined.
Conclusions:
- CK2 remains a paradoxical enzyme with significant implications in cancer.
- Understanding CK2's precise role and its flexible phosphoproteome is crucial for developing targeted cancer therapies.
- Despite challenges, CK2 represents a viable therapeutic target in oncology.
Related Concept Videos
01:19Counterfactual Thinking
03:20The Stanford Prison Experiment
01:38Limits to Natural Selection
02:20Dynamic Equilibrium
00:57Deindividuation
01:28Conditions of Equilibrium
Internal forces are not considered for conditions of equilibrium because they occur in equal and opposite pairs within the body, effectively canceling each other. As a result,...