title: Exploring the CK2 Paradox: Restless, Dangerous, Dispensable.
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.
authors.affiliation: Department of Biomedical Sciences, University of Padova, via U. Bassi, 58/B, 35131 Padova, Italy. cinzia.franchin@unipd.it.|Proteomics Center, University of Padova and Azienda Ospedaliera di Padova, via G. Orus, 2/B, 35129 Padova, Italy. cinzia.franchin@unipd.it.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Franchin
authors.affiliation: Department of Biomedical Sciences, University of Padova, via U. Bassi, 58/B, 35131 Padova, Italy. christian.borgo@unipd.it.
authors.forename: Christian
authors.initials: C
authors.lastname: Borgo
authors.affiliation: Proteomics Center, University of Padova and Azienda Ospedaliera di Padova, via G. Orus, 2/B, 35129 Padova, Italy. silviazaramella7@gmail.com.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zaramella
authors.affiliation: Department of Biomedical Sciences, University of Padova, via U. Bassi, 58/B, 35131 Padova, Italy. luca.cesaro.1@unipd.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Cesaro
authors.affiliation: Department of Biomedical Sciences, University of Padova, via U. Bassi, 58/B, 35131 Padova, Italy. giorgio.arrigoni@unipd.it.|Proteomics Center, University of Padova and Azienda Ospedaliera di Padova, via G. Orus, 2/B, 35129 Padova, Italy. giorgio.arrigoni@unipd.it.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arrigoni
authors.affiliation: Department of Biomedical Sciences, University of Padova, via U. Bassi, 58/B, 35131 Padova, Italy. mauro.salvi@unipd.it.
authors.forename: Mauro
authors.initials: M
authors.lastname: Salvi
authors.affiliation: Department of Biomedical Sciences, University of Padova, via U. Bassi, 58/B, 35131 Padova, Italy. lorenzo.pinna@unipd.it.|CNR Neurosciences Institute, via U. Bassi, 58/B, 35131 Padova, Italy. lorenzo.pinna@unipd.it.
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Pinna
keywords: CRISPR/Cas9 technology; cancer; casein kinase 2; non oncogene addiction; phosphoproteomics; protein kinase CK2; signal transduction