A potential role of nuclear matrix-associated protein kinase CK2 in protection against drug-induced apoptosis in cancer cells.
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 CK2alpha or CK2alphabeta showed significant resistance to chemical-mediated apoptosis commensurate with the corresponding elevation in CK2 in the NM. Transfection with CK2beta 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.
Guo
C
C
Department of Laboratory Medicine and Pathology and University of Minnesota Cancer Center, University of Minnesota and the Department of Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA.
Yu
S
S
Davis
A T
AT
Wang
H
H
Green
J E
JE
Ahmed
K
K
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D017209:Apoptosis; D047390:Casein Kinase II; D020134:Catalytic Domain; D002451:Cell Compartmentation; D019610:Cytoprotection; D003600:Cytosol / Q000201:enzymology; D004273:DNA, Neoplasm / Q000032:analysis; D004054:Diethylstilbestrol / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy; D051379:Mice; D015530:Nuclear Matrix / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011994:Recombinant Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology
D004273:DNA, Neoplasm; D011994:Recombinant Proteins; D005047:Etoposide; D004054:Diethylstilbestrol; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases