Abstract
Casein Kinase 2 \(\alpha\) (CK2\(\alpha\)) expression is found to be upregulated in various cancers and it is correlated with the sustenance of undifferentiated malignant phenotype and promotion of metastasis. This study aims to investigate the role of OGR1, a metastasis suppressor gene, in regulating the expressions of CK2\(\alpha\) genes; CSNK2A1 and CSNK2A3 (intronless) in K562 cells (Chronic Myelogenous Leukemia cell line) differentiation. When phorbol 12-myristate 13-acetate (PMA) is treated to induce differentiation of K562 cells into megakaryocytic cells, the expression of OGR1 is upregulated whereas the expressions of CSNK2A3 and CSNK2A1 are downregulated. Interestingly, OGR1 overexpression alone can induce differentiation of K562 similar to PMA and also downregulates the expression of CSNK2A3. However, it upregulates the expression of CSNK2A1. The results indicate that the downregulation of CSNK2A3 is necessary or required for K562 differentiation. OGR1 differentially regulates the expressions of CSNK2A3 and CSNK2A1. Activation of G \(\alpha\) i, involvement of monomeric G-proteins, and p38 pathway are seen in the OGR1 regulation of CSNK2A1 and CSNK2A3 expression. Therefore, it can be concluded that OGR1 and CSNK2A3 may be the key regulators of megakaryocytic differentiation.
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References
Ahmad KA, Wang G, Slaton J, Unger G, Ahmed K (2005) Targeting CK2 for cancer therapy. Anticancer Drugs 16(10):1037–1043
Ahmed K, Gerber DA, Cochet C (2002) Joining the cell survival squad: an emerging role for protein kinase CK2. Trends Cell Biol 12(5):226–230
Chua MM, Ortega CE, Sheikh A, Lee M, Abdul-Rassoul H, Hartshorn KL, Dominguez I (2017) CK2 in cancer: cellular and biochemical mechanisms and potential therapeutic target. Pharmaceuticals 10(1):18
Devilat I, Carvallo P (1993) Structure and sequence of an intronless gene for human casein kinase II-α subunit. FEBS Lett 316(2):114–118
Dominguez I, Sonenshein GE, Seldin DC (2009) Protein kinase CK2 in health and disease. Cell Mol Life Sci 66(11):1850–1857
Gocek E, Marcinkowska E (2011) Differentiation therapy of acute myeloid leukemia. Cancers 3(2):2402–2420
Gowda C, Sachdev M, Muthusami S, Kapadia M, Petrovic-Dovat L, Hartman M et al (2017) Casein kinase II (CK2) as a therapeutic target for hematological malignancies. Curr Pharm Des 23(1):95–107
Guerra B, Issinger OG (2008) Protein kinase CK2 in human diseases. Curr Med Chem 15(19):1870–1886
Guerra B, Issinger OG (1999) Protein kinase CK2 and its role in cellular proliferation, development, and pathology. ELECTROPHORESIS: Int J 20(2):391–408
Hung MS, Lin YC, Mao JH, Kim IJ, Xu Z, Yang CT et al (2010) Functional polymorphism of the CK2a intronless gene plays oncogenic roles in lung cancer
Kang H, Jung JW, Kim MK, Chung JH (2009) CK2 is the regulator of SIRT1 substrate-binding affinity, deacetylase activity, and cellular response to DNA-damage. PLoS ONE 4(8):e6611
Lee SW, Song YS, Lee SY, Yoon YG, Lee SH, Park BS et al (2011) Downregulation of protein kinase CK2 activity facilitates tumor necrosis factor-α-mediated chondrocyte death through apoptosis and autophagy. PloS one 6(4):e19163
Lian H, Su M, Zhu Y, Zhou Y, Soomro SH, Fu H (2019) Protein kinase CK2, a potential therapeutic target in carcinoma management. Asian Pac J Cancer Prev: APJCP 20(1):23
Losa JH, Cobo CP, Viniegra JG, Lobo VJSA, Sanchez-Prieto R (2003) Role of the p38 MAPK pathway in cisplatin-based therapy. Oncogene 22(26):3998-4006
Ludwig MG, Vanek M, Guerini D, Gasser JA, Jones CE, Junker U et al (2003) Proton-sensing G-protein-coupled receptors. Nature, 425(6953):93–98
Manni S, Brancalion A, Tubi LQ, Colpo A, Pavan L, Cabrelle A et al (2012) Protein kinase CK2 protects multiple myeloma cells from ER stress–induced apoptosis and from the cytotoxic effect of hsp90 inhibition through regulation of the unfolded protein response. Clin Cancer Res 18(7):1888–1900
Meggio F, Pinna LA (2003) One-thousand-and-one substrates of protein kinase CK2? FASEB J 17(3):349–368
Mitrovský O, Myslivcová D, Macháčková-Lopotová T, Obr A, Čermáková K, Ransdorfová Š et al (2021). Inhibition of casein kinase 2 induces cell death in chronic myelogenous leukemia cells with different mechanisms of resistance to tyrosine kinase inhibitors. bioRxiv
Montenarh M (2010) Cellular regulators of protein kinase CK2. Cell Tissue Res 342(2):139–146
Olsen BB, Svenstrup TH, Guerra B (2012) Downregulation of protein kinase CK2 induces autophagic cell death through modulation of the mTOR and MAPK signaling pathways in human glioblastoma cells. Int J Oncol 41(6):1967–1976
Olson JM, Hallahan AR (2004) p38 MAP kinase: a convergence point in cancer therapy. Trends Mol Med 10(3):125–129
Ono K, Han J (2000) The p38 signal transduction pathway activation and function. Cell Signal 12(1):1–13
Piazza FA, Ruzzene M, Gurrieri C, Montini B, Bonanni L, Chioetto G et al (2006) Multiple myeloma cell survival relies on high activity of protein kinase CK2. Blood 108(5):1698–1707
Sharma AL, Meitei PM, Machathoibi TC, Singh NT, Singh TR, Singh LS (2022) Ovarian cancer G protein-coupled receptor 1 inhibits A549 cells migration through casein kinase 2α intronless gene and neutral endopeptidase. BMC Cancer 22(1):1–12
Singh LS, Kalafatis M (2002) Sequencing of full-length cDNA encoding the α and β subunits of human casein kinase II from human platelets and megakaryocytic cells. Expression of the casein kinase IIα intronless gene in a megakaryocytic cell line. Biochemistry 41(28):8935–8940
Singh LS, Berk M, Oates R, Zhao Z, Tan H, Jiang Y et al (2007) Ovarian cancer G protein-coupled receptor 1, a new metastasis suppressor gene in prostate cancer. J Natl Cancer Inst 99(17):1313–1327
Trembley JH, Chen Z, Unger G, Slaton J, Kren BT, Van Waes C, Ahmed K (2010) The emergence of protein kinase CK2 as a key target in cancer therapy. BioFactors 36(3):187–195
Wang G, Unger G, Ahmad KA, Slaton JW, Ahmed K (2005) Downregulation of CK2 induces apoptosis in cancer cells–a potential approach to cancer therapy. Mol Cell Biochem 274(1):77–84
Wirkner U, Pyerin W (1999) CK2α loci in the human genome: structure and transcriptional activity. In: A molecular and cellular view of protein kinase CK2, pp 59–64
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Singh, N.T., Meitei, P.M., Singh, L.S. (2023). Roles of Metastasis Suppressor Gene, OGR1 and Casein Kinase 2\(\alpha\) Intronless Gene, CSNK2A3 in Megakaryocytic Differentiation. In: Pandey, L.M., Gupta, R., Thummer, R.P., Kar, R.K. (eds) Healthcare Research and Related Technologies. NERC 2022. Springer, Singapore. https://doi.org/10.1007/978-981-99-4056-1_3
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