Significance of protein kinase CK2 nuclear signaling in neoplasia

Abstract

Many stimuli play a role in in¯uencing the structure and function of chromatin and nuclear matrix through post-translational modi®cations of the component proteins in these dynamic structures. We propose that the protein serine/threonine kinase CK2 (formerly casein kinase II) is one such agent that is involved in signal transduction in the nuclear matrix and chromatin in response to a variety of stimuli. Protein kinase CK2 appears to undergo rapid modulations in its association with nuclear matrix and nucleosomes in response to mitogenic signals and is involved in the phosphorylation of a variety of intrinsic proteins in these structures depending on the state of genomic activity. In addition, its association or loss from the nuclear matrix may also in¯uence the apoptotic activity in the cell. CK2 has been found to be dysregulated in virtually all the neoplasias examined and nuclear association appears to be an important facet of its expression in tumor cells. We hypothesize that CK2 provides a functional paradigm linking the nuclear matrix and chromatin structures. Identi®cation of precise loci of action of CK2 in these structures and how they in¯uence the morphological appearance of the nucleus under normal and abnormal growth conditions would be an important future direction of investigation.

Protein kinase CK2 – A key suppressor of apoptosis

“…a These authors made equal contribution. b Present address: Northwestern Health Sciences University, Bloomington, MN both the nuclear and cytoplasmic compartments in the cell, and undergoes dynamic shuttling between various compartments which may relate to its functional activity in those compartments (Ahmed et al, 1993;Ahmed, 1994a, 1994b;Tawfic et al, 1996Tawfic et al, , 1997Guo et al, 1998Guo et al, , 1999aGuo et al, , 1999bAhmed et al, 2000;Faust and Montenarh, 2000). A key feature of CK2 cell biology is that it is essential for cell survival (e.g., Padmanabha et al, 1990), and accordingly, attempts to produce CK2-knockout mice have been unsuccessful (Bouchou et al, 2003).…”

“…The β subunits in turn may form a linkage with the nuclear matrix (Zhang et al, 1998) which is a key locus for CK2 signaling in the nucleus (Ahmed, 1999). The growth related functions of CK2 accord with CK2-mediated phosphorylation of a rather large number of substrates in the cell, many of which are nuclear-associated and are involved in gene expression and cell growth (for recent reviews see e.g., Ahmed et al, 2000;Tawfic et al, 2001;Ahmed et al, 2002;Pinna, 2002;Litchfield, 2003;Pyerin and Ackermann, 2003). The kinase is localized to cCorresponding author, to whom all communications should be sent at: ahmedk@umn.edu.…”

“…Regulation of cellular CK2 appears to be complex and various hypotheses have been proposed on this subject (for reviews, see e.g., Allende and Allende, 1995;Ahmed, 1999;Montenarh and Faust, 2000;Pinna, 2002;Filhol et al, 2004;Olsten et al, 2005). To explain some of our data on CK2 responses to altered cell growth, we originally proposed that CK2 undergoes dynamic shuttling between cytoplasm and nucleus and further within the nucleus it undergoes differential distribution depending on the conditions to which the cell is exposed (Ahmed et al, 1993;Ahmed, 1999;Ahmed, 1994a, 1994b;Tawfic et al, 1996Tawfic et al, , 1997Guo et al, 1998Guo et al, , 1999aGuo et al, , 1999bAhmed et al, 2000). Subsequently, it was demonstrated that CK2 translocation can take place to other parts of the cell further reinforcing the notion that dynamic intracellular shuttling of CK2 might represent a key mode of its regulation in the cell in response to diverse signals (Tawfic et al, 1997;Faust and Montenarh, 2000).…”

Structural and functional insights into the regulation mechanism of CK2 by IP 6 and the intrinsically disordered protein Nopp140

“…Casein kinase 2 (CK2) is a ubiquitous protein kinase that is essential for cell growth (2), development, and other essential cellular processes (3)(4)(5)(6)(7). More than 300 proteins that are involved in DNA replication, transcription, translation, and signal transduction are phosphorylated by CK2 (8).…”

Urokinase-dependent Human Vascular Smooth Muscle Cell Adhesion Requires Selective Vitronectin Phosphorylation by Ectoprotein Kinase CK2

“…The definition of this problem is strengthened by the findings of others indicating that the actual level of CK2 expression and activity in a given cell type is very specific. Thus, even a small deviation would produce an altered or dysregulated biological response in the cell (29). This conclusion is supported by our results demonstrating that although uPA increased Vn phosphorylation and VSMC adhesion up to 3-fold, the calculated stoichiometry of this reaction was relatively low and corresponded to 0.42 mmol of phosphate per mol of Vn.…”