Protein kinase CK2 (CK2) has long been implicated in the regulation of cell growth and proliferation. Its activity is generally elevated in rapidly proliferating tissues, and nuclear matrix (NM) is an important subnuclear locale of its functional signaling. In the prostate, nuclear CK2 is rapidly lost commensurate with induction of receptor-mediated apoptosis after growth stimulus withdrawal. By contrast, chemical-induced apoptosis in prostate cancer and other cells (by etoposide and diethylstilbestrol) evokes an enhancement in CK2 associated with the NM that appears to be because of translocation of CK2 from the cytoplasmic to the nuclear compartment. This shuttling of CK2 to the NM may reflect a protective response to chemical-mediated apoptosis. Supporting evidence for this was obtained by employing cells that were transiently transfected with various expression plasmids of CK2 (thereby expressing additional CK2) prior to treatment with etoposide or diethylstilbestrol. Cells transfected with the CK2␣ or CK2␣␤ showed significant resistance to chemical-mediated apoptosis commensurate with the corresponding elevation in CK2 in the NM. Transfection with CK2␤ did not demonstrate this effect. These results suggest, for the first time, that besides the commonly appreciated function of CK2 in cell growth, it may also have a role in protecting cells against apoptosis. Protein kinase CK2 (CK2)1 has been extensively studied in recent years for its potential role in multiple functional activities including the regulation of cell growth and proliferation. It is a ubiquitous protein Ser/Thr kinase, localized in the cell cytoplasm and nucleus, existing as a heterotetramer consisting of ␣, ␣Ј, and ␤ subunits (ϳ 42, 38, and 28 kDa, respectively) with the possible ␣ 2 ␤ 2 , ␣␣Ј␤ 2 , or ␣Ј␣Ј␤ 2 configuration. A number of putative substrates for CK2 have been identified in both the cytoplasm and the nucleus. Many of these are based on in vitro phosphorylation studies although a number of them have also been shown to be substrates for CK2 in vivo. Among the nuclear substrates are proteins involved in growth including RNA polymerases, topoisomerase II, protein B23, nucleolin, SV40 large T antigen, certain proto-oncogene products, and growth factors, as well as certain nonhistone proteins, which might include transcription factors, etc. (for examples see Refs. 1-10).In previous work, we have demonstrated that CK2 is dynamically regulated with respect to its nuclear localization, such that chromatin and NM appear to be its preferential sites of association within the nucleus. The association of CK2 in these compartments is profoundly responsive to the status of growth stimuli (1, 9, 11-13). 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. It is well known that withdrawal of androgenic growth signal via castration of adult rats induces rapid apoptosis in the epithelial cells of the gland and that this process is reversed on andro...

Medications delivered in the prehospital care of children were frequently administered outside of the proper dose range when compared with patient weights recorded in the prehospital medical record. EMS systems should develop strategies to reduce pediatric medication dosing errors.

Anakinra could represent a promising therapeutic approach in these life-threatening disorders that are likely underdiagnosed and often difficult to treat.