These preliminary data reveal that malignant transformation of the upper aerodigestive tract mucosa is associated with altered CK2 activity. The results further suggest that dysregulation of this protein kinase may play a significant role in the pathobiology of SCCHN, and that CK2 activity may be a prognostic indicator in this malignancy.

Protein B23 is a nucleolar and nuclear matrix-associated phosphoprotein that is involved in ribosome synthesis. Its expression and phosphorylation in rat ventral prostate, an androgen target organ, are profoundly influenced by androgens. Induction of programmed cell death (apoptosis) in the prostatic epithelium by androgen deprivation in the animal induces an early decline in protein B23 in the absence of a corresponding loss of protein B23 mRNA. We have now demonstrated that prostatic nuclei retain the ability to transcribe the B23 mRNA and that a significant amount of this mRNA persists even after 7 days of androgen deprivation when >80% of the prostatic epithelial cells have undergone apoptosis. The B23 mRNA from these nuclei is also translatable in vitro. However, the majority of the B23 mRNA is associated with free and short-stretch polysomes, which may account for the castration-induced decline in synthesis of protein B23 in vivo. In addition, the mechanism of down-regulation of protein B23 in apoptotic prostatic cells appears to relate to two coordinate signals, which include loss of phosphorylation of the protein as well as the expression of a protease active toward dephosphorylated protein B23, under these conditions.Programmed cell death or apoptosis has been described in diverse biological systems mediated by a variety of signals (1-3), and the response of the prostatic glandular epithelium to androgen withdrawal is one of the frequently studied models (3, 4). Androgen withdrawal via orchiectomy in the rat induces an energy-dependent cascade of biochemical and morphological changes that lead to the death of 80% of the secretory epithelium between days 2 and 6 (4). Morphologically, the nucleolus dissolves (5), and the chromatin is condensed and fragmented to form the membrane-bound apoptotic bodies that appear in appreciable numbers after 2 days of androgen deprivation (6). Biochemically, there is an increase in intracellular calcium and enhancement of calcium/magnesium-dependent endonuclease activity that reaches its maximum 4 -5 days after androgen withdrawal (7). Apoptosis in the prostate is associated with modulation of gene expression so that the expression of some genes is repressed and that of others is enhanced. Among the latter are c-fos, c-myc, heat shock proteins (8), glutathione S-transferase (9), and TRPM-2/sulfated glycoproteins (10). On the other hand, the synthesis of ribosomes, especially their assembly into polysomes, markedly declines after androgen deprivation (11,12). Also, prostatic ribosomes from animals treated with 5␣-dihydrotestosterone support a significantly higher incorporation of radiolabeled amino acids into proteins than do ribosomes isolated from castrated animal controls (11).We have been interested in the mechanisms underlying the decline in prostatic rRNA synthesis and assembly after androgen deprivation. Protein B23, a conserved phosphoprotein that is localized to the granular and fibrillar regions of the nucleolus where rRNA synthesis and assembly take place (13, 1...

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.

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