Abstract

Protein kinase CK2 has been implicated in control of cell growth and proliferation. Since growth stimuli evoke its preferential association with chromatin and nuclear matrix, we examined the dynamics of CK2 in nucleosomes fractionated on the basis of their transcriptional activity in the rat prostate. In this model, androgens induce expression of androgen-dependent genes but inhibit the androgen-repressed genes, whereas absence of androgens has the reverse effect. The level of CK2 was higher in the active than in inactive nucleosomes from normal prostate. Differential alterations in the levels of CK2 activity in the transcriptionally active versus inactive nucleosomes were evoked by androgen deprivation or administration. Comparison of the distribution of CK2 in active and inactive nucleosomes under varying androgenic conditions showed that the relative CK2 activity intrinsic to the transcriptionally active nucleosomes remained fairly stable, concordant with gene activity specific to the androgenic status. However, CK2 associated with inactive nucleosomes declined to a minimal level on androgen deprivation but increased rapidly on androgen administration (reflecting expression of multiple androgen-dependent genes). We suggest a role for CK2 in promoting the conformational transition of inactive nucleosomes to the active form and in the function of transcriptionally active nucleosomes.

Highlights

  • CK2 appears to be dynamically regulated with respect to its nuclear localization [7, 8] which is manifested by its preferential association with chromatin and nuclear matrix [7, 9, 10]

  • The association of CK2 with these compartments is modulated in response to growth stimuli (7, 9 –12) which is of interest since both chromatin and nuclear matrix play fundamental roles in genomic activity and cell proliferation

  • Androgenic stimulation evokes early expression of genes such as C3 and, over time, of a large number of prostatic androgen-dependent genes, whereas the androgen-repressed genes are suppressed [25,26,27]. These markers can be used to differentiate the type of nucleosomes isolated from prostatic tissue under varied androgenic conditions. We have used this paradigm previously to demonstrate that CK2 is preferentially associated with the chromatin and nuclear matrix fractions isolated from purified nuclei and that this association is dynamically regulated in a spatiotemporal manner in response to altered androgenic status [7, 9, 11, 12]

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Summary

Introduction

CK2 appears to be dynamically regulated with respect to its nuclear localization [7, 8] which is manifested by its preferential association with chromatin and nuclear matrix [7, 9, 10]. Androgenic stimulation evokes early expression of genes such as C3 and, over time, of a large number of prostatic androgen-dependent genes, whereas the androgen-repressed genes are suppressed [25,26,27] These markers can be used to differentiate the type of nucleosomes isolated from prostatic tissue under varied androgenic conditions. We have used this paradigm previously to demonstrate that CK2 is preferentially associated with the chromatin and nuclear matrix fractions isolated from purified nuclei and that this association is dynamically regulated in a spatiotemporal manner in response to altered androgenic status [7, 9, 11, 12]. Dynamics of Protein Kinase CK2 in Nucleosomes inactive nucleosomes suggesting a possible role for CK2 in nucleosome organization and function

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