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

Channavajhala, Padmalatha; Seldin, David C.

doi:10.1038/sj.onc.1205640

Cited by 142 publications

(99 citation statements)

References 48 publications

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“…For example, in studies on TRAIL mediated induction of apoptosis, we observed downregulation of cFLIP L which was prevented by overexpression of CK2 in PC-3 prostate cancer cells (Wang et al, 2006a); the significance of this observation may relate to the recent documentation that cFLIP L expression is necessary and sufficient to maintain resistance to TRAIL-induced apoptosis in prostate cancer cells (Zhang et al, 2004). Upon phosphorylation by CK2, Max is rendered insensitive to cleavage by caspases (Krippner-Heidenreich et al, 2001) while Myc is stabilized by CK2 mediated phosphorylation (Channavajhala and Seldin, 2002). In the NF-κB pathway, downregulation of CK2 by employing antisense CK2α resulted in nuclear translocation of NF-κB p65 (Ahmad et al, 2006).…”

Section: Downstream Targets Of Ck2 In the Apoptotic Machinerymentioning

confidence: 49%

Protein kinase CK2 – A key suppressor of apoptosis

Ahmad

Wang

Unger

et al. 2008

Advances in Enzyme Regulation

232

188

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Section: Downstream Targets Of Ck2 In the Apoptotic Machinerymentioning

confidence: 49%

Protein kinase CK2 – A key suppressor of apoptosis

Ahmad

Wang

Unger

et al. 2008

Advances in Enzyme Regulation

232

188

View full text Add to dashboard Cite

“…2D) and TBB (4,5,6,7-tetrabromo-2-azabenzimidazole; IC 50 : 0.9 mM) (Fig. 2E) [39,40]. The analyses revealed that the CK2 inhibitors Apigenin and TBB were able to efficiently suppress Thr 244 phosphorylation Fig.…”

Section: Resultsmentioning

confidence: 90%

“…The analyses revealed that the CK2 inhibitors Apigenin and TBB were able to efficiently suppress Thr 244 phosphorylation Fig. 2D and E) [39,40]. Thus, CK2 appears to be the protein kinase that targets APRIL Thr 244 .…”

Section: Resultsmentioning

confidence: 94%

Phosphorylation of the HuR ligand APRIL by casein kinase 2 regulates CD83 expression

et al. 2009

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Fully mature DC and, to a lesser extent, activated T and B cells express CD83, a surface molecule that appears to fulfil an important role in efficient T-cell activation. Recently, it has been shown that CD83 mRNA is transported from the nucleus to the cytoplasm by an uncommon route, involving the cellular RNA-binding protein HuR and the nuclear export receptor CRM1. Moreover, the shuttle phosphoprotein APRIL (ANP32B) has been shown to be required for HuR-mediated nucleocytoplasmic translocation of the CD83 mRNA by acting as an adaptor that links HuR and CRM1. Here, we are able to report that casein kinase 2 (CK2) phosphorylates APRIL on residue threonine244 (Thr 244 ) and demonstrate that the CK2-specific inhibitor 4,5,6,7-tetrabromo-2-azabenzimidazole abolishes CD83 expression in activated Jurkat T cells by interfering with the nucleocytoplasmic translocation of CD83 mRNA. Depletion and knockdown studies demonstrate that the CK2 a 0 subunit is necessary for this regulation, whereas the CK2 a subunit seems to be dispensable. Taken together, the data presented significantly extend our knowledge of the complex regulation of CD83 mRNA processing and provides a novel strategy to interfere with CD83 expression.Key words: APRIL . Casein kinase 2 . CD83 . HuR . Leukocytes IntroductionMature DC are capable of sensitizing even naïve CD4 1 and CD8 1 T cells, and are therefore frequently termed ''nature's adjuvant''. Immature DC reside in the peripheral tissues and upon uptake of antigen and exposure to inflammatory stimuli, they migrate to the peripheral lymph nodes, where now fully matured, they induce antigen-specific T-cell response [1][2][3][4]. The DC maturation process includes the modulation of chemokine and chemokine receptors, as well as the up-regulation of several cytokines, costimulatory and adhesion molecules [5].Human CD83 serves as a major marker molecule for mature DC that belongs to the immunoglobulin super family [6,7]. This membrane-bound protein is also expressed, although to a significant lower extent, on activated T and B cells [7][8][9][10]. Moreover, a soluble form of CD83 is detectable at low levels in sera derived from healthy individuals, whereas in contrast, elevated levels are present in patients suffering from certain hematological malignancies [8,11]. Notwithstanding the fact that accumulating experimental evidence suggests that CD83 plays an important functional role in the regulation of DCmediated T-cell-specific immune response [12][13][14][15][16][17][18][19], the exact function of CD83 remains poorly understood [20][21][22]. Nevertheless, various disease-related findings suggest that CD83 holds great potential for future therapeutic application [23]. For example, EAE can be prevented in mice by applying a soluble form of CD83 [24]. Likewise, in rats, a positive therapeutic effect on experimental autoimmune myasthenia gravis has been reported by application of pentoxifylline, a drug that apparently interferes with CD83 expression [25,26]. Furthermore, CD83 1 DC were found to localize i...

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“…37 Parallel and subsequent work demonstrated in this model that CK2 cooperates both with loss of the tumor suppressor p53 and with overexpression of the oncogene c-myc in causing lymphocyte proliferation and clonal expansion. 38,39 These initial studies established a proliferative and apoptosis-protective role for CK2 in T lymphocyte in the mouse. However, a more straightforward role of this kinase in lymphocyte oncogenesis has been recently suggested by studies in human lymphoid tumors, both arising from precursor cells and from mature lymphocytes.…”

Section: Ck2 In Lymphoid Tumors Mouse Modelsmentioning

confidence: 99%

Protein kinase CK2 in hematologic malignancies: reliance on a pivotal cell survival regulator by oncogenic signaling pathways

et al. 2012

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CK2 is a multitask kinase whose role is essential for a countless number of cellular processes, many of which are critical for blood cell development. A prevailing task for this kinase rests on counteracting programmed cell death triggered by multiple stimuli. CK2 is overexpressed in many solid tumors and in vivo mouse models have proven its tumorigenic potential. Recent data have suggested that CK2 may also have a significant role in the pathogenesis of hematopoietic tumors, such as multiple myeloma, chronic lymphocytic leukemia, acute myelogenous leukemia, acute lymphoblastic leukemia and chronic myeloproliferative neoplasms. CK2 regulates hematopoiesis-associated signaling pathways and seems to reinforce biochemical cascades indispensable for tumor growth, proliferation and resistance to conventional and novel cytotoxic agents. Although its activity is multifold, recent evidence supports the rationale of CK2 inhibition as a therapeutic strategy in solid and hematological tumors and phase-I clinical trials are in progress to test the efficacy of this innovative therapeutic approach. 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. Leukemia (2012Leukemia ( ) 26, 1174Leukemia ( --1179 doi:10.1038/leu.2011; published online 13 January 2012Keywords: hematopoiesis; blood tumors; protein kinase CK2; kinase inhibitors INTRODUCTION Protein kinase CK2 is a highly conserved pleiotropic acidophilic serine-threonine kinase whose essential role in several cellular processes has been increasingly appreciated over the last decade. 1 Structurally, CK2 is a tetrameric enzyme, composed by the assembly of two catalytic (a and/or a') and two regulatory b subunits. The catalytic and regulatory subunits may also be present in the cell as unassembled molecules and it seems that this state is associated with distinct and specific functions. The two catalytic subunits a and a' share 90% sequence homology in their N-terminal region. The regulatory subunit b instead does not have any similarity to the other two subunits. 2 CK2 recognizes motifs characterized by a S/T N-terminal to acidic amino acids, its minimum consensus being S/T-X-X-Ac, where X is any amino acid and Ac is a residue with a carboxylic or phosphorylated side chain (E, D, pS, pY).The spectrum of actions of this kinase is impressive as it can phosphorylate hundreds of substrate proteins, which are involved in disparate cellular processes, such as regulation of cell structure, division, proliferation, programmed death, DNA damage repair, protein translation, gene transcription, organelle function and so forth. 3 It has been estimated that a substantial proportion of the human phosphoproteome (up to 20%) is generated by CK2 alone. For this reason, CK2 has long been viewed as a 'non-targetable' kinase for therapeutic purposes.The essential role of CK2 for cell and organism life is underscored by th...

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

Cited by 142 publications

References 48 publications

Protein kinase CK2 – A key suppressor of apoptosis

Protein kinase CK2 – A key suppressor of apoptosis

Phosphorylation of the HuR ligand APRIL by casein kinase 2 regulates CD83 expression

Protein kinase CK2 in hematologic malignancies: reliance on a pivotal cell survival regulator by oncogenic signaling pathways

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