Association of casein kinase 2 with nuclear chromatin in relation to androgenic regulation of rat prostate.

Abstract

Casein kinase 2 (CK-2) is a ubiquitous messenger-independent protein serine/threonine kinase that has been implicated in growth control. We have studied the activity and subcelular location of CK-2 in adult rat ventral prostate in relation to androgen withdrawal and administration. Androgen deprivation by castration results in a faster decline in CK-2 activity associated with prostatic nuclei than that in the cytosol. Nuclear CK-2 associated with chromatin is reduced at an even greater rate than that in the total nucleus. Reversal of these events by administration of a single dose of 5a-dihydrotestosterone to adult rats castrated 144 hr previously was accompanied by a differential early enhancement of chromatin-associated CK-2 activity, with a concomitant decrease in the CK-2 activity present in the cytosol. Changes in the nuclear CK-2 activity correlated with the immunostainable enzyme protein in the nucleus. We propose that androgens evoke translocation of CK-2 from the cytoplasm to the nucleus (nucleoplasm) where its enhanced association with the chromatin constituents takes place. Conversely, withdrawal of circulating androgens due to castration evokes a dissociation of CK-2 from chromatin and eventual translocation of nucleoplasmic CK-2 to the cytoplasm. Modulations in the association of CK-2 with nuclear chromatin may represent an important mechanism of post-transcriptional regulation of nuclear CK-2 in relation to androgen action in the prostate.Protein phosphorylation/dephosphorylation represents a major mechanism of mediation of cellular functions. The vast family ofknown protein kinases catalyzes phosphorylation of a multitude of proteins in the cell in response to various stimuli. Although cellular regulation of certain protein kinases is achieved through second messengers, the control mechanisms for the regulation of protein kinases that are not activated by any known second messenger are generally not well understood (1, 2). Casein kinases are a group of messenger-independent protein serine/threonine kinases found ubiquitously in eukaryotic cells. Casein kinase 1 (CK-1) and casein kinase 2 (CK-2), isolated from nuclear and cytosolic sources, have been well characterized. CK-2 is composed of three subunits of 42, 38, and 28 kDa, existing as a, a', and 32 configuration. Much work has implicated it in the phosphorylation of various cellular protein substrates, such as nuclear nonhistone proteins, certain oncoproteins, RNA polymerases, topoisomerases, steroid receptors, various factors involved in protein synthesis machinery, etc., leading to the proposal that CK-2 plays a role in cell growth and proliferation (see, e.g., refs. 1-6).Rat ventral prostate is a male accessory sex gland whose growth and functions are strictly dependent on androgens whose actions are largely mediated through regulation of transcriptional activity (7-10). We have employed androgen action on rat ventral prostate as an experimental model in our studies on the relation of CK-2 to growth control and have shown that phosph...

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).…”

“…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).…”

“…On the other hand, when growth stimulus was instituted by androgen administration in animals previously deprived of androgens there was a rapid shuttling of CK2 to the nuclear compartment of prostate epithelial cells prior to cell growth. Noteworthy was the observation that the translocated CK2 was differentially associated with the chromatin and nuclear matrix fractions in the nucleus (Ahmed et al, 1993;Tawfic and Ahmed, 1994b;Guo et al, 1998;Ahmed, 1999;Tawfic et al, 2001). Removal of growth factors from the culture media resulted in shuttling of CK2 from the nuclear to the cytoplasmic compartment and subsequent addition of the growth factors to the culture media demonstrated a reversal of this process with CK2 shuttling to the nucleus (Guo et al, 1999a).…”

Live-Cell Fluorescence Imaging Reveals the Dynamics of Protein Kinase CK2 Individual Subunits

“…FCS analysis also provides evidence for the existence of a subpopulation of slowmoving CK2 subunits that could represent integral components of less mobile structures, such as nuclear matrix or chromosome scaffold. Interestingly, a rapid translocation of CK2 to nuclear matrix associated with genomic activation upon induction of cell growth has been described in an in vivo physiological model (2,19). It could be also imagined that the previously described reversible polymerization of CK2 subunits (41) might also create transient, less-mobile nuclear complexes.…”

A Potential Role of Nuclear Matrix-associated Protein Kinase CK2 in Protection against Drug-induced Apoptosis in Cancer Cells

“…The association of CK2 in these compartments is profoundly responsive to the status of growth stimuli (1,9,(11)(12)(13). To that end, we have employed androgen action in the prostate epithelial cells that is mediated via the androgen-receptor system as an experimental model.…”