casein kinase ii

Summary

Summary: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.

Top Publications

  1. Parsons J, Dianova I, Finch D, Tait P, Ström C, Helleday T, et al. XRCC1 phosphorylation by CK2 is required for its stability and efficient DNA repair. DNA Repair (Amst). 2010;9:835-41 pubmed publisher
    ..We therefore propose that CK2 plays an important role in DNA repair by contributing to the stability of XRCC1-Lig III complex. ..
  2. Bandyopadhyay K, Gjerset R. Protein kinase CK2 is a central regulator of topoisomerase I hyperphosphorylation and camptothecin sensitivity in cancer cell lines. Biochemistry. 2011;50:704-14 pubmed publisher
  3. Turowec J, Duncan J, French A, Gyenis L, St Denis N, Vilk G, et al. Protein kinase CK2 is a constitutively active enzyme that promotes cell survival: strategies to identify CK2 substrates and manipulate its activity in mammalian cells. Methods Enzymol. 2010;484:471-93 pubmed publisher
    ..Collectively, the methods that are presented in this chapter should enable the identification and characterization of CK2 substrates and CK2-regulated processes both in vitro and in living cells. ..
  4. Nguyen L, Mitchell B. Akt activation enhances ribosomal RNA synthesis through casein kinase II and TIF-IA. Proc Natl Acad Sci U S A. 2013;110:20681-6 pubmed publisher
    ..We have found that activated Akt enhances rRNA synthesis through the phosphorylation of casein kinase II? (CK2?) on a threonine residue near its N terminus...
  5. Siddiqui Jain A, Bliesath J, Macalino D, Omori M, Huser N, Streiner N, et al. CK2 inhibitor CX-4945 suppresses DNA repair response triggered by DNA-targeted anticancer drugs and augments efficacy: mechanistic rationale for drug combination therapy. Mol Cancer Ther. 2012;11:994-1005 pubmed publisher
    ..These data position CK2 as a valid pharmacologic target for intelligent drug combinations and support the evaluation of CX-4945 in combination with gemcitabine and platinum-based chemotherapeutics in the clinical setting. ..
  6. Wang H, Yang Y, Sharma N, Tarasova N, Timofeeva O, Winkler Pickett R, et al. STAT1 activation regulates proliferation and differentiation of renal progenitors. Cell Signal. 2010;22:1717-26 pubmed publisher
    ..These findings show that both metanephric progenitors and renal tumor cells utilize a STAT1-dependent mechanism for growth or survival. ..
  7. Pierre F, Chua P, O Brien S, Siddiqui Jain A, Bourbon P, Haddach M, et al. Pre-clinical characterization of CX-4945, a potent and selective small molecule inhibitor of CK2 for the treatment of cancer. Mol Cell Biochem. 2011;356:37-43 pubmed publisher
    ..In vivo time-dependent reduction in the phosphorylation of the biomarker p21 at T145 was observed by immunohistochemistry. Inhibition of the newly validated CK2 target by CX-4945 represents a fresh therapeutic strategy for cancer. ..
  8. Brachet A, Leterrier C, Irondelle M, Fache M, Racine V, Sibarita J, et al. Ankyrin G restricts ion channel diffusion at the axonal initial segment before the establishment of the diffusion barrier. J Cell Biol. 2010;191:383-95 pubmed publisher
    ..In conclusion, our findings indicate that specific binding to ankG constitutes the initial step for Nav channel immobilization at the AIS membrane and precedes the establishment of the diffusion barrier. ..
  9. Trembley J, Chen Z, Unger G, Slaton J, Kren B, Van Waes C, et al. Emergence of protein kinase CK2 as a key target in cancer therapy. Biofactors. 2010;36:187-95 pubmed publisher
    ..Thus, appropriate strategies to target CK2 especially by molecular approaches may lead to a highly feasible and effective approach to eradication of a given cancer. ..

More Information

Publications62

  1. Lambert I, Hansen D. Regulation of taurine transport systems by protein kinase CK2 in mammalian cells. Cell Physiol Biochem. 2011;28:1099-110 pubmed publisher
    ..Furthermore, we discuss how CK2-mediated regulation of taurine homeostasis is potentially involved in cellular functions such as proliferation and survival. ..
  2. Battistutta R, Cozza G, Pierre F, Papinutto E, Lolli G, Sarno S, et al. Unprecedented selectivity and structural determinants of a new class of protein kinase CK2 inhibitors in clinical trials for the treatment of cancer. Biochemistry. 2011;50:8478-88 pubmed publisher
    ..735 and 0.755, respectively, vs 0.615), marking the highest selectivity ever reported for CK2 inhibitors. ..
  3. Gil C, Falqués A, Sarró E, Cubi R, Blasi J, Aguilera J, et al. Protein kinase CK2 associates to lipid rafts and its pharmacological inhibition enhances neurotransmitter release. FEBS Lett. 2011;585:414-20 pubmed publisher
    ..In conclusion, CK2 might control neurotransmitter release by acting on SNARE proteins attached to cholesterol-enriched microdomains. ..
  4. Hung M, Lin Y, Mao J, Kim I, Xu Z, Yang C, et al. Functional polymorphism of the CK2alpha intronless gene plays oncogenic roles in lung cancer. PLoS ONE. 2010;5:e11418 pubmed publisher
    ..These results are consistent with an important role for the 398T allele of the CSNK2A1P in human lung cancer susceptibility. ..
  5. Willems S, Schrage Y, Bruijn I, Szuhai K, Hogendoorn P, Bovee J. Kinome profiling of myxoid liposarcoma reveals NF-kappaB-pathway kinase activity and casein kinase II inhibition as a potential treatment option. Mol Cancer. 2010;9:257 pubmed publisher
  6. Barrett R, Colnaghi R, Wheatley S. Threonine 48 in the BIR domain of survivin is critical to its mitotic and anti-apoptotic activities and can be phosphorylated by CK2 in vitro. Cell Cycle. 2011;10:538-48 pubmed
    ..To our knowledge these data are the first to identify T48 as a key regulatory site on survivin, and CK2 as a mediator of its mitotic and anti-apoptotic functions. ..
  7. Bischoff N, Olsen B, Raaf J, Bretner M, Issinger O, Niefind K. Structure of the human protein kinase CK2 catalytic subunit CK2?' and interaction thermodynamics with the regulatory subunit CK2?. J Mol Biol. 2011;407:1-12 pubmed publisher
    ..Taken together, CK2?' exhibits a significantly lower affinity for CK2? than CK2?; moreover, in functionally critical regions, it is less dependent on CK2? to obtain a fully functional conformation. ..
  8. Jia H, Liu Y, Xia R, Tong C, Yue T, Jiang J, et al. Casein kinase 2 promotes Hedgehog signaling by regulating both smoothened and Cubitus interruptus. J Biol Chem. 2010;285:37218-26 pubmed publisher
    ..We showed that CK2 prevents Ci ubiquitination and degradation by the proteasome. Thus, CK2 promotes Hh signaling activity by regulating multiple pathway components. ..
  9. Ryu B, Baek S, Kim J, Bae S, Chang S, Heo J, et al. Anti-androgen receptor activity of apoptotic CK2 inhibitor CX4945 in human prostate cancer LNCap cells. Bioorg Med Chem Lett. 2012;22:5470-4 pubmed publisher
    ..Pharmacologic inhibition experiment revealed that CX4945 could exhibit its anti-cancer activity in LNCap cells via the independent inhibitions of AR and Akt-survivin signalings. ..
  10. Ponce D, Maturana J, Cabello P, Yefi R, Niechi I, Silva E, et al. Phosphorylation of AKT/PKB by CK2 is necessary for the AKT-dependent up-regulation of ?-catenin transcriptional activity. J Cell Physiol. 2011;226:1953-9 pubmed publisher
    ..Taken together, the data suggest that the CK2?-dependent up-regulation of ?-catenin activity requires phosphorylation of AKT in human embryonic kidney cells. ..
  11. Piazza F, Manni S, Ruzzene M, Pinna L, Gurrieri C, Semenzato G. Protein kinase CK2 in hematologic malignancies: reliance on a pivotal cell survival regulator by oncogenic signaling pathways. Leukemia. 2012;26:1174-9 pubmed publisher
    ..In this review, we will summarize the data supporting CK2 as an oncogenic kinase in blood tumors and we will describe some critical signaling pathways, whose regulation by this protein kinase may be implicated in tumorigenesis. ..
  12. Graczyk D, Debski J, Muszynska G, Bretner M, Lefebvre O, Boguta M. Casein kinase II-mediated phosphorylation of general repressor Maf1 triggers RNA polymerase III activation. Proc Natl Acad Sci U S A. 2011;108:4926-31 pubmed publisher
    ..We report that phosphorylation of Maf1 by casein kinase II (CK2), a highly evolutionarily conserved eukaryotic kinase, is required for efficient Pol III transcription...
  13. Pierre F, Chua P, O Brien S, Siddiqui Jain A, Bourbon P, Haddach M, et al. Discovery and SAR of 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic acid (CX-4945), the first clinical stage inhibitor of protein kinase CK2 for the treatment of cancer. J Med Chem. 2011;54:635-54 pubmed publisher
    ..25n was found to be highly selective, orally bioavailable across species (20-51%) and efficacious in xenograft models. The discovery of 25n will allow the therapeutic targeting of CK2 in humans for the first time. ..
  14. Siddiqui Jain A, Drygin D, Streiner N, Chua P, Pierre F, O Brien S, et al. CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy. Cancer Res. 2010;70:10288-98 pubmed publisher
    ..Finally, CX-4945 is the first orally bioavailable small molecule inhibitor of CK2 to advance into human clinical trials, thereby paving the way for an entirely new class of targeted treatment for cancer. ..
  15. Zou J, Luo H, Zeng Q, Dong Z, Wu D, Liu L. Protein kinase CK2? is overexpressed in colorectal cancer and modulates cell proliferation and invasion via regulating EMT-related genes. J Transl Med. 2011;9:97 pubmed publisher
    ..Our results indicate that CK2? plays an essential role in the development of CRC, and inhibition of CK2? may serve as a promising therapeutic strategy for human CRC. ..
  16. Ruzzene M, Di Maira G, Tosoni K, Pinna L. Assessment of CK2 constitutive activity in cancer cells. Methods Enzymol. 2010;484:495-514 pubmed publisher
  17. Sanz Clemente A, MATTA J, Isaac J, Roche K. Casein kinase 2 regulates the NR2 subunit composition of synaptic NMDA receptors. Neuron. 2010;67:984-96 pubmed publisher
    ..Thus, CK2 plays a central role in determining the NR2 subunit content of synaptic NMDARs. ..
  18. Cozza G, Meggio F, Moro S. The dark side of protein kinase CK2 inhibition. Curr Med Chem. 2011;18:2867-84 pubmed
  19. Sawada H, Yamahama Y, Yamamoto T, Togawa T, Mase K. Developmental changes in the localization of protein kinase CK2 in non-diapause and diapause eggs of the silkworm, Bombyx mori. Zoolog Sci. 2012;29:6-10 pubmed publisher
    ..These data suggest that the role of BmCK2 is different in non-diapause and diapause eggs. ..
  20. Salvi M, Trashi E, Marin O, Negro A, Sarno S, Pinna L. Superiority of PLK-2 as ?-synuclein phosphorylating agent relies on unique specificity determinants. Biochem Biophys Res Commun. 2012;418:156-60 pubmed publisher
  21. Bliesath J, Huser N, Omori M, Bunag D, Proffitt C, Streiner N, et al. Combined inhibition of EGFR and CK2 augments the attenuation of PI3K-Akt-mTOR signaling and the killing of cancer cells. Cancer Lett. 2012;322:113-8 pubmed publisher
    ..Taken together, these data position CK2 as a valid pharmacologic target for drug combinations and support further evaluation of CX-4945 in combination with EGFR targeting agents. ..
  22. Ponce D, Yefi R, Cabello P, Maturana J, Niechi I, Silva E, et al. CK2 functionally interacts with AKT/PKB to promote the ?-catenin-dependent expression of survivin and enhance cell survival. Mol Cell Biochem. 2011;356:127-32 pubmed publisher
    ..Therefore, our results strongly suggest that CK2?-specific enhancement of ?-catenin transcriptional activity as well as cell survival may depend on AKT hyperactivation by CK2. ..
  23. Lin K, Tai C, Hsu J, Li C, Fang C, Lai H, et al. Overexpression of nuclear protein kinase CK2 ? catalytic subunit (CK2?) as a poor prognosticator in human colorectal cancer. PLoS ONE. 2011;6:e17193 pubmed publisher
    ..The data indicated that CK2?-specific siRNA treatment resulted in growth inhibition. Taken together, overexpression of nuclear CK2? can be a useful marker for predicting the outcome of patients with CRC. ..
  24. Prudent R, Moucadel V, Nguyen C, Barette C, Schmidt F, Florent J, et al. Antitumor activity of pyridocarbazole and benzopyridoindole derivatives that inhibit protein kinase CK2. Cancer Res. 2010;70:9865-74 pubmed publisher
    ..Our work lays the foundation for development of clinically useful CK2 inhibitors derived from a well-studied scaffold with suitable pharmacokinetics parameters. ..
  25. Sun Z, Ren H, Liu Y, Teeling J, Gu J. Phosphorylation of RIG-I by casein kinase II inhibits its antiviral response. J Virol. 2011;85:1036-47 pubmed publisher
    ..Threonine at amino acid (aa) 770 and serine at aa 854 to 855 of RIG-I are phosphorylated by casein kinase II (CK2) in the resting state of the cell and dephosphorylated when cells are infected by RNA virus...
  26. Schneider C, Ampofo E, Montenarh M. CK2 regulates ATF4 and CHOP transcription within the cellular stress response signalling pathway. Cell Signal. 2012;24:1797-802 pubmed publisher
    ..ATF4 is involved in ER stress signalling through the AARE, which further supports our finding that CK2 inhibition provokes an amino acid induced response pathway. ..
  27. Yoo J, Choi H, Choi K, Park S, Ota I, Yook J, et al. Nuclear hormone receptor corepressor promotes esophageal cancer cell invasion by transcriptional repression of interferon-?-inducible protein 10 in a casein kinase 2-dependent manner. Mol Biol Cell. 2012;23:2943-54 pubmed
    ..Collectively these data suggest that the CK2?-NCoR cascade selectively represses the transcription of IP-10 and promotes oncogenic signaling in human esophageal cancer cells. ..
  28. Lolli G, Cozza G, Mazzorana M, Tibaldi E, Cesaro L, Donella Deana A, et al. Inhibition of protein kinase CK2 by flavonoids and tyrphostins. A structural insight. Biochemistry. 2012;51:6097-107 pubmed
    ..As in the case of luteolin, the pyrocatechol group of AG99 is critical for binding, interacting with the positive area in the deepest part of the CK2 active site. ..
  29. Cozza G, Pinna L, Moro S. Protein kinase CK2 inhibitors: a patent review. Expert Opin Ther Pat. 2012;22:1081-97 pubmed publisher
    ..However, in the last 5 years an increasing number of patents on CK2 inhibitors have been registered, reflecting an increased interest in this kind of drug candidates and their possible therapeutic applications. ..
  30. Martins L, Lucio P, Silva M, Anderes K, Gameiro P, Silva M, et al. Targeting CK2 overexpression and hyperactivation as a novel therapeutic tool in chronic lymphocytic leukemia. Blood. 2010;116:2724-31 pubmed publisher
    ..Overall, our study indicates that CK2 plays a critical role in CLL cell survival, laying the groundwork for the inclusion of CK2 inhibitors into future therapeutic strategies. ..
  31. Ruzzene M, Tosoni K, Zanin S, Cesaro L, Pinna L. Protein kinase CK2 accumulation in "oncophilic" cells: causes and effects. Mol Cell Biochem. 2011;356:5-10 pubmed publisher
    ..We show in particular that persistence of high CK2 level in R-CEM, as opposed to S-CEM, is accompanied by the presence of an immunospecific form of Cdc37 not detectable in S-CEM and refractory to staurosporine-induced degradation. ..
  32. Hanif I, Hanif I, Shazib M, Ahmad K, Pervaiz S. Casein Kinase II: an attractive target for anti-cancer drug design. Int J Biochem Cell Biol. 2010;42:1602-5 pubmed publisher
    b>Casein Kinase II (CK2) is a ubiquitous serine/threonine kinase that is highly conserved in eukaryotic cells. CK2 has been shown to impact cell growth and proliferation, as numerous growth-related proteins are substrates of CK2...
  33. Raaf J, Bischoff N, Klopffleisch K, Brunstein E, Olsen B, Vilk G, et al. Interaction between CK2? and CK2?, the subunits of protein kinase CK2: thermodynamic contributions of key residues on the CK2? surface. Biochemistry. 2011;50:512-22 pubmed publisher
    The protein Ser/Thr kinase CK2 (former name: casein kinase II) exists predominantly as a heterotetrameric holoenzyme composed of two catalytic subunits (CK2?) bound to a dimer of noncatalytic subunits (CK2?)...
  34. St Denis N, Bailey M, Parker E, Vilk G, Litchfield D. Localization of phosphorylated CK2alpha to the mitotic spindle requires the peptidyl-prolyl isomerase Pin1. J Cell Sci. 2011;124:2341-8 pubmed publisher
    ..Furthermore, because Pin1 has many important spindle substrates, this might represent a general mechanism for localization of mitotic signalling proteins. ..
  35. Hessenauer A, Schneider C, Götz C, Montenarh M. CK2 inhibition induces apoptosis via the ER stress response. Cell Signal. 2011;23:145-51 pubmed publisher
    ..We show that this ER stress response led to an up-regulation of the death receptor DR5 and subsequent apoptosis in LNCaP cells. ..
  36. Giusiano S, Cochet C, Filhol O, Duchemin Pelletier E, Secq V, Bonnier P, et al. Protein kinase CK2? subunit over-expression correlates with metastatic risk in breast carcinomas: quantitative immunohistochemistry in tissue microarrays. Eur J Cancer. 2011;47:792-801 pubmed publisher
  37. Hanif I, Pervaiz S. Repressing the activity of protein kinase CK2 releases the brakes on mitochondria-mediated apoptosis in cancer cells. Curr Drug Targets. 2011;12:902-8 pubmed
    ..Here we provide a brief review of CK2-mediated inhibition of mitochondrial death signaling in cancer cells and its implications for the design of novel target specific therapeutic strategies. ..
  38. Duncan J, Turowec J, Duncan K, Vilk G, Wu C, Luscher B, et al. A peptide-based target screen implicates the protein kinase CK2 in the global regulation of caspase signaling. Sci Signal. 2011;4:ra30 pubmed publisher
    ..Together, these data support a role for CK2-dependent phosphorylation as a global mechanism for inhibiting caspase signaling pathways. ..
  39. Mollapour M, Tsutsumi S, Truman A, Xu W, Vaughan C, Beebe K, et al. Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity. Mol Cell. 2011;41:672-81 pubmed publisher
    ..Overexpression of Aha1 stimulates the ATPase activity, restores cochaperone interactions, and compensates for the functional defects of these Hsp90 mutants. ..
  40. Chang C, Naik M, Huang Y, Jeng J, Liao P, Kuo H, et al. Structural and functional roles of Daxx SIM phosphorylation in SUMO paralog-selective binding and apoptosis modulation. Mol Cell. 2011;42:62-74 pubmed publisher
    ..Our findings provide structural insights into the Daxx-SIM:SUMO-1 complex, a model of SIM phosphorylation-enhanced SUMO paralog-selective modification and interaction, and phosphorylation-regulated Daxx function in apoptosis. ..
  41. Perea S, Baladron I, Garcia Y, Perera Y, López A, Soriano J, et al. CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research. Mol Cell Biochem. 2011;356:45-50 pubmed publisher
    ..Collectively, our data outline important clues on translational and clinical research from this novel peptide-based drug reinforcing its perspectives to treat cancer and paving the way to validate CK2 as a promising target in oncology. ..
  42. Hosoi T, Korematsu K, Horie N, Suezawa T, Okuma Y, Nomura Y, et al. Inhibition of casein kinase 2 modulates XBP1-GRP78 arm of unfolded protein responses in cultured glial cells. PLoS ONE. 2012;7:e40144 pubmed publisher
    ..Immunohistochemical analysis suggested that CK2 was present at the ER. These results indicate CK2 to be linked with UPR and to resist ER stress by activating the XBP-1-GRP78 arm of UPR. ..
  43. Zhang S, Wang Y, Mao J, Hsieh D, Kim I, Hu L, et al. Inhibition of CK2? down-regulates Hedgehog/Gli signaling leading to a reduction of a stem-like side population in human lung cancer cells. PLoS ONE. 2012;7:e38996 pubmed publisher
    ..Thus, we report that the inhibition of CK2? down-regulates Hh/Gli signaling and subsequently reduces stem-like side population in human lung cancer cells...
  44. Deshiere A, Duchemin Pelletier E, Spreux E, Ciais D, Combes F, Vandenbrouck Y, et al. Unbalanced expression of CK2 kinase subunits is sufficient to drive epithelial-to-mesenchymal transition by Snail1 induction. Oncogene. 2013;32:1373-83 pubmed publisher
    ..This study also suggests that unbalanced expression of CK2 subunits may drive EMT, thereby contributing to tumour progression. ..
  45. Perez D, Gil C, Martinez A. Protein kinases CK1 and CK2 as new targets for neurodegenerative diseases. Med Res Rev. 2011;31:924-54 pubmed publisher
    ..The role of these two kinases in the molecular pathology of different neurodegenerative diseases together with different chemical families that are able to more or less specifically inhibit CK1 and CK2 are discussed in this review. ..
  46. Zheng Y, Qin H, Frank S, Deng L, Litchfield D, Tefferi A, et al. A CK2-dependent mechanism for activation of the JAK-STAT signaling pathway. Blood. 2011;118:156-66 pubmed publisher
    ..Our data provide evidence for novel cross-talk between CK2 and JAK-STAT signaling, with implications for therapeutic intervention in JAK2V617F-positive MPDs. ..
  47. Moucadel V, Prudent R, Sautel C, Teillet F, Barette C, Lafanechere L, et al. Antitumoral activity of allosteric inhibitors of protein kinase CK2. Oncotarget. 2011;2:997-1010 pubmed
    ..Azonaphthalene compounds are allosteric CK2 inhibitors showing antitumor activity. CK2 may be targeted allosterically. These inhibitors provide a foundation for a new paradigm for specific CK2 inhibition. ..
  48. Tripodi F, Cirulli C, Reghellin V, Marin O, Brambilla L, Schiappelli M, et al. CK2 activity is modulated by growth rate in Saccharomyces cerevisiae. Biochem Biophys Res Commun. 2010;398:44-50 pubmed publisher
    ..Also in chemostat cultures nuclear CK2 activity is higher in faster growing cells providing the first unequivocal demonstration that growth rate itself can affect CK2 activity in a eukaryotic organism. ..
  49. Mollapour M, Tsutsumi S, Kim Y, Trepel J, Neckers L. Casein kinase 2 phosphorylation of Hsp90 threonine 22 modulates chaperone function and drug sensitivity. Oncotarget. 2011;2:407-17 pubmed
    ..We also provide evidence that T22 is an important determinant of Hsp90 inhibitor sensitivity in yeast and we show that T22 phosphorylation status contributes to drug sensitivity in vivo. ..
  50. Yefi R, Ponce D, Niechi I, Silva E, Cabello P, Rodriguez D, et al. Protein kinase CK2 promotes cancer cell viability via up-regulation of cyclooxygenase-2 expression and enhanced prostaglandin E2 production. J Cell Biochem. 2011;112:3167-75 pubmed publisher
    ..Altogether, these findings provide new insight to the role of CK2 in cancer by up-regulating COX-2 expression and thereby PGE2 production. ..
  51. Sarno S, Papinutto E, Franchin C, Bain J, Elliott M, Meggio F, et al. ATP site-directed inhibitors of protein kinase CK2: an update. Curr Top Med Chem. 2011;11:1340-51 pubmed
  52. Hagan C, Regan T, Dressing G, Lange C. ck2-dependent phosphorylation of progesterone receptors (PR) on Ser81 regulates PR-B isoform-specific target gene expression in breast cancer cells. Mol Cell Biol. 2011;31:2439-52 pubmed publisher
  53. Bandyopadhyay K, Li P, Gjerset R. CK2-mediated hyperphosphorylation of topoisomerase I targets serine 506, enhances topoisomerase I-DNA binding, and increases cellular camptothecin sensitivity. PLoS ONE. 2012;7:e50427 pubmed publisher