Subcellular immunolocalization of protein kinase CK2 in normal and carcinoma cells

Faust, Russell A.; Niehans, Gloria A.; Gapany, M.; Hoistad, Dick L.; Knapp, Dennis; Cherwitz, David L.; Davis, Alan T.; Adams, George L.; Ahmed, Khalil

doi:10.1016/s1357-2725(99)00050-3

Cited by 69 publications

(59 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In many human cancers examined, as well as in experimental tumors, CK2 activity has been found to be consistently elevated (Munstermann et al, 1990;Faust et al, 1999;Landesman-Bollag et al, 2001). Upregulation of CK2 in tumors is consistent with a role for CK2 in cell growth promotion or in the inhibition of apoptosis.…”

Section: Discussionmentioning

confidence: 57%

“…It comprises two catalytic a or a 0 subunits and two regulatory b subunits that can form a holoenzyme (Allende and Allende, 1995). In many human cancers that have been examined, as well as experimental tumors, CK2 activity has been found to be consistently enhanced (Munstermann et al, 1990;Faust et al, 1999;Landesman-Bollag et al, 2001). This upregulation of CK2 in tumors is consistent with a role for CK2 in growth promotion, cellular transformation or in inhibiting apoptosis, although the latter still remains to be fully established.…”

Section: Introductionmentioning

confidence: 64%

See 1 more Smart Citation

Casein kinase II (CK2) enhances death-inducing signaling complex (DISC) activity in TRAIL-induced apoptosis in human colon carcinoma cell lines

et al. 2005

View full text Add to dashboard Cite

Protein kinase casein kinase II (CK2) is increased in response to diverse growth stimuli, as well as being elevated in many human cancers examined. We have demonstrated that CK2 is a key survival factor that protects human colon carcinoma cells from TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. We determined that inhibition of CK2 phosphorylation events by DRB (5,6-dichlorobenzimidazole) resulted in dramatic sensitization of tumor cells to TRAIL-induced apoptosis, in the absence of effects in normal cells. Sensitization was caspase dependent, and independent of regulation via NF-jB. Further, inhibition of phosphorylation by CK2 did not modify the expression level of antiapoptotic proteins. Analysis of TRAIL-induced deathinducing signaling complex (DISC) formation demonstrated enhanced formation of the DISC, enhanced cleavage of caspase-8 and cleavage of Bid in the presence of DRB, thereby facilitating the release of proapoptotic factors from the mitochondria with subsequent downregulation of the expression of XIAP and c-IAP1. Further, silencing of CK2a in HT29 cells following transfection of CK2a shRNA abrogated CK2 kinase activity while simultaneously increasing TRAIL sensitivity. These findings demonstrate that CK2 plays a critical antiapoptotic role by conferring resistance to TRAIL at the level of the DISC.

show abstract

Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 64%

Casein kinase II (CK2) enhances death-inducing signaling complex (DISC) activity in TRAIL-induced apoptosis in human colon carcinoma cell lines

et al. 2005

View full text Add to dashboard Cite

show abstract

“…It has been well documented that PKCK2 is involved in the regulation of apoptosis by phosphorylating some apoptosis-related factors. PKCK2 activity has been found to be consistently enhanced in various tumor cells (42)(43)(44), and increased expression of PKCK2 has protected cells against Fas-and drug-induced apoptosis (45,46). Furthermore, inhibitors of PKCK2 have been reported to trigger apoptosis and increase the susceptibility of cancer cells to chemotherapeutic agents or apoptotic stimuli (47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

Cilostazol protects rat chondrocytes against nitric oxide–induced apoptosis in vitro and prevents cartilage destruction in a rat model of osteoarthritis

Lee

Song

Shin

et al. 2008

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To examine whether cilostazol, a selective phosphodiesterase type III inhibitor, protects rat articular chondrocytes against nitric oxide (NO)-induced apoptosis and prevents cartilage destruction in mono-iodoacetate-induced osteoarthritis (OA) in a rat model in which inducible nitric oxide synthase (iNOS) is expressed.Methods. The NO donor sodium nitroprusside was administered to rat articular chondrocytes that had been pretreated with cilostazol. Induction of apoptosis was evaluated by DNA electrophoresis and pulsed-field gel electrophoresis. The expression level and the subcellular location of apoptosis-associated factors were examined by Western blot analysis and confocal microscopy, respectively. Protein kinase CK2 (PKCK2) activity was also assayed. To examine whether orally administered cilostazol prevents cartilage destruction in vivo, cartilage samples obtained from rats with experimentally induced OA were subjected to hematoxylin and eosin, Safranin O, and TUNEL staining and immunohistochemical analysis of iNOS expression.Results. Cilostazol prevented NO-induced reduction in viability, in a dose-dependent manner. It also prevented the up-regulation of phosphorylated p53 and p38, the down-regulation of heme oxygenase 1, the subcellular translocation of apoptosis-inducing factor and cytochrome c, and the activation of caspases 3, 7, and 8 induced by NO treatment, indicating that cilostazol prevented NO-induced cell death by blocking apoptosis. In addition, cilostazol prevented NO-induced translocation of cleaved Bid onto mitochondria, and caused phosphorylated Bid to accumulate in the nucleus and cytosol. Cilostazol prevented the down-regulation of PKCK2 and the reduction in PKCK2 activity induced by NO, indicating that its apoptosis-preventing activity was mediated via PKCK2. It also prevented chondrocyte apoptosis and cartilage destruction in a rat model of experimentally induced OA. Conclusion. Our findings indicate that cilostazol prevents NO-induced apoptosis of chondrocytes via PKCK2 in vitro and prevents cartilage destruction in a rat model of OA.

show abstract

“…Dysregulated CK2 protein expression was first reported in a bovine pseudo-leukemia caused by a protozoan parasite (ole-MoiYoi et al, 1992). A series of additional papers have documented its upregulation in many human cancers including leukemias (Daya-Makin et al, 1994;Faust et al, 1996;Gapany et al, 1995), and solid tumors (Faust et al, 1996(Faust et al, , 1999Munstermann et al, 1990) including breast cancer (Landesman-Bollag et al, 2001). We have utilized transgenic mice to demonstrate that dysregulated expression of CK2 contributes to lymphocyte transformation (Seldin and Leder, 1995).…”

Section: Introductionmentioning

confidence: 96%

Functional interaction of protein kinase CK2 and c-Myc in lymphomagenesis

2002

View full text Add to dashboard Cite

Protein kinase CK2 (formerly casein kinase II) is frequently upregulated in human cancers, and transgenic expression of CK2a in lymphocytes is oncogenic. Lymphomagenesis is dramatically acclerated by coexpression of a c-myc transgene, suggestive of a synergistic interaction between the kinase and the transcription factor. Since c-myc can be phosphorylated by CK2, we hypothesized that the synergy between CK2 and c-myc might be due to a functional interaction of the two molecules. Pharmacologic inhibition of CK2 activity in cell lines established from CK2a transgenic T cell lymphomas reduces their proliferation and concomitantly with this, the steady state levels of c-myc protein decline. This is caused by acclerated c-myc protein turnover, which occurs in a proteasome-dependent manner. Transfection of cells with sense or anti-sense CK2 constructs modulates c-myc protein levels in concert with the alteration in CK2 activity, validating the findings obtained using the kinase inhibitors. Thus, CK2 is a critical regulator of c-myc protein stability and of the proliferation of these T cell lymphomas.

show abstract

Subcellular immunolocalization of protein kinase CK2 in normal and carcinoma cells

Cited by 69 publications

References 19 publications

Casein kinase II (CK2) enhances death-inducing signaling complex (DISC) activity in TRAIL-induced apoptosis in human colon carcinoma cell lines

Casein kinase II (CK2) enhances death-inducing signaling complex (DISC) activity in TRAIL-induced apoptosis in human colon carcinoma cell lines

Cilostazol protects rat chondrocytes against nitric oxide–induced apoptosis in vitro and prevents cartilage destruction in a rat model of osteoarthritis

Functional interaction of protein kinase CK2 and c-Myc in lymphomagenesis

Contact Info

Product

Resources

About