Protein kinase CK2 and its role in cellular proliferation, development and pathology

Pharmacological inhibition of protein kinase CK2 reverts the multidrug resistance phenotype of a CEM cell line characterized by high CK2 level

“…CK2 phosphorylates a huge number of protein substrates, involved in many fundamental cell processes (Meggio and Pinna, 2003), and is essential for cell life. It is frequently upregulated in human cancers (Guerra and Issinger, 1999), and transgenic expression of CK2a in lymphocytes is oncogenic (Seldin and Leder, 1995) and accelerates leukemia development induced by other oncogenes (Kelliher et al, 1996). Recently, a global anti-apoptotic role of CK2 has been disclosed (reviewed by Ahmed et al, 2002;Litchfield, 2003), whose mechanism is seemingly multifactorial and only partly understood.…”

Bovine prion protein as a modulator of protein kinase CK2

“…Nevertheless, a few functions have been proposed : for example, an involvement in anti-apoptotic pathways [26] or in the cellular resistance to oxidative stress exploited by the combined superoxide dismutase activity and copperbinding capacity of PrP c [27,28]. Our results disclose another possible function of PrP, by showing that bPrP interacts with and up-regulates one of the most pleiotropic protein kinases, CK2, known to impinge on many proteins implicated in a variety of cell functions, in particular in signal transduction and gene expression pathways [1,8,29]. It is noteworthy that CK2 is also widely exploited by infectious agents, such as viruses and parasites, to perform the phosphorylation of proteins essential to their life cycle [29].…”

“…Our results disclose another possible function of PrP, by showing that bPrP interacts with and up-regulates one of the most pleiotropic protein kinases, CK2, known to impinge on many proteins implicated in a variety of cell functions, in particular in signal transduction and gene expression pathways [1,8,29]. It is noteworthy that CK2 is also widely exploited by infectious agents, such as viruses and parasites, to perform the phosphorylation of proteins essential to their life cycle [29]. Although CK2 is almost ubiquitous, it is especially abundant in the brain [30], where it is present in all the regions studied [31].…”

p53-dependent inhibition of mammalian cell survival by a genetically selected peptide aptamer that targets the regulatory subunit of protein kinase CK2

“…There is mounting evidence that the two CK2 subunits can exist in their free form outside the tetrameric complex (Bibby and Litchfield, 2005;Filhol et al, 2004). For instance, more than 40 different proteins were shown to interact with CK2b, and importantly, this protein was characterized as a regulatory binding partner of several protein kinases involved in cell signalling (Guerra and Issinger, 1999). Disruption of CK2b in transgenic mice has revealed the importance of this regulatory protein in the maintenance of cell proliferation and cell viability (Buchou et al, 2003).…”

“…However, this traditional view has been challenged by the evidence for naturally occurring free monomeric CK2a (Dobrowolska et al, 1992;Stigare et al, 1993;Heriche et al, 1997) and for an unbalanced expression of CK2 subunits in different mammalian tissues (Stalter et al, 1994;Pinna and Meggio, 1997;Guerra et al, 1999b;Ghavidel and Schultz, 2001;Keller et al, 2001). Moreover, the marked elevation of CK2 enzymatic activity in various solid tumors is suspected to result in the suppression of cellular apoptosis, aiding tumor resistance to radiation and anticancer drug treatments (Guerra and Issinger, 1999;Ahmed et al, 2002).…”