Urokinase-induced mitogenesis is mediated by casein kinase 2 and nucleolin

Dumler, Inna; Stepanova, Victoria; Jerke, Uwe; Mayboroda, Oleg A.; Vogel, Frank; Bouvet, Philippe; Tkachuk, Vsevolod A.; Haller, Hermann; Gulba, Dietrich C.

doi:10.1016/s0960-9822(00)80116-5

Cited by 84 publications

(68 citation statements)

References 54 publications

(75 reference statements)

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“…Other investigators have shown that nucleolin can be found on the cell surface (24,(27)(28)(29)(30)(31)(32)(33)(34). Nucleolin can interact with the IKVAV site of laminin, which is a major component of basement membranes (35,36).…”

Section: Discussionmentioning

confidence: 99%

An Acidic Peptide Sequence of Nucleolin-Related Protein Can Mediate the Attachment of Calcium Oxalate to Renal Tubule Cells

Сорокина¹,

Wesson²,

Kleinman³

2004

Journal of the American Society of Nephrology

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Abstract. Crystals that form in tubular fluid must be retained in the kidney to become stones. Nucleolin-related protein (NRP) is found on the surface of inner medullary collecting duct (IMCD) cells in culture (cIMCD) and selectively adsorbs to calcium oxalate (CaOx). We proposed that NRP mediates attachment to the renal tubular epithelium of Ca stone crystals through an electrostatic interaction with a highly acidic region (acidic fragment [AF]) similar to those of other proteins that have been reported to affect urinary crystal formation. The current studies demonstrate that nucleolin is expressed on both apical and basolateral cell surfaces of cIMCD, reaching a peak in the late stages of mitosis and gradually declining to undetectable levels with maturation of the polarized epithelium. Scraping areas of mature monolayers stimulated the cells surrounding the defects to migrate and proliferate so as to repair them, and these areas demonstrate surface NRP expression and enhanced attachment of CaOx monohydrate crystals. Surface expression of the NRP AF was produced by cloning the NRP AF into a display vector. Transfected cIMCD demonstrating copious surface expression of AF enhanced CaOx attachment 6.7-fold compared with control cIMCD, whereas cells transfected with a vector without the AF did not differ from control. AF was also cloned into a replication-deficient adenovirus and expressed in 293 cells, resulting in AF secretion into the nutrient medium. This medium inhibited CaOx attachment to cIMCD, compared with conditioned medium from cells infected with wild-type virus. These results demonstrate that surface-bound AF can mediate CaOx attachment and that secreted AF can inhibit attachment. These results support the notion that surface-associated NRP could mediate attachment of CaOx to the renal tubule epithelium, thereby causing retention of crystals that might eventually become kidney stones.Several groups of investigators have suggested that an important early event in the formation of kidney stones is the attachment of calcium oxalate (CaOx) crystals to the apical surface of renal tubular epithelium (1-3). Well-polarized, undisturbed tubular epithelial cells in culture demonstrate little capacity for crystal attachment (4 -6). This resistance to attachment may be due to the confinement of molecules with crystal-binding properties to domains other than the apical membrane. When tight junctions between cells are disrupted in the course of cellular proliferation or migration or when cells are exposed to a number of different agents, apical membranes seem to express constituents with affinity for CaOx.Nucleolin-related protein (NRP) is a surface-associated protein of cultured inner medullary collecting duct (IMCD) cells that selectively adsorbs to CaOx and binds to membrane skeletal elements in a Ca-dependent manner (7). NRP has a highly acidic region composed of 62% Asp and Glu residues (135KNGKNAKKEDSDEEDDDDSEEEDEEDEDEEDEFE PTVMKAAAAAPAS-DEEEDDEEDDDEDDDEEDEDED-EDDSEEEAMETTPAKGKKAPVKAVPVKAKSTAEE-DEEEDDEDEEDDEE...

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Section: Discussionmentioning

confidence: 99%

An Acidic Peptide Sequence of Nucleolin-Related Protein Can Mediate the Attachment of Calcium Oxalate to Renal Tubule Cells

Сорокина¹,

Wesson²,

Kleinman³

2004

Journal of the American Society of Nephrology

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“…Later, Dumler et al (18) demonstrated co-internalization of the uPAR⅐nucleolin complex inside the cell, which emphasizes the possibility of nuclear translocation of uPAR. We show that IR-induced overexpression of uPAR leads to uPAR translocation in the nucleus and its association with different transcription factors that may facilitate maintenance of stemness.…”

mentioning

confidence: 97%

Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Regulation of WNT/β-Catenin Signaling Is Enhanced in Irradiated Medulloblastoma Cells

Asuthkar

Gondi

Nalla

et al. 2012

Journal of Biological Chemistry

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Background: uPAR is a multifunctional protein, overexpressed in all human cancers. Results: uPAR overexpression with radiation enhances ␤-catenin stabilization, ␤-catenin gene transcription, and WNT-7a-␤-catenin-TCF/LEF-mediated transactivation. Conclusion: Association of uPAR with ␤-catenin and various transcription factors involved in embryonic development suggests that uPAR is a potent activator of cancer stemness. Significance: Targeting uPAR in cancer patients undergoing radiotherapy will have favorable therapeutic implications.

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“…In addition, nucleolin has been implicated, directly or indirectly, in other roles including nuclear matrix structure (19), DNA replication (20), cytokinesis and nuclear division (21), and as a nucleic acid helicase (12,22). There have been numerous reports describing the presence of nucleolin in the plasma membrane of cells (9,(23)(24)(25)(26)(27)(28), suggesting a further * This work was supported by the Department of Defense Prostate Cancer Initiative, the National Institutes of Health, and the Commonwealth of Kentucky Research Challenge Trust. The costs of publication of this article were defrayed in part by the payment of page charges.…”

mentioning

confidence: 99%

Inhibition of DNA Replication and Induction of S Phase Cell Cycle Arrest by G-rich Oligonucleotides

Hamhouyia²,

Thomas³

et al. 2001

Journal of Biological Chemistry

154

161

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The discovery of G-rich oligonucleotides (GROs) that have non-antisense antiproliferative activity against a number of cancer cell lines has been recently described. This biological activity of GROs was found to be associated with their ability to form stable G-quartet-containing structures and their binding to a specific cellular protein, most likely nucleolin (Bates, P. J., Kahlon, J. B., Thomas, S. D., Trent, J. O., and Miller, D. M. (1999) J. Biol. Chem. 274, 26369 -26377). In this report, we further investigate the novel mechanism of GRO activity by examining their effects on cell cycle progression and on nucleic acid and protein biosynthesis. Cell cycle analysis of several tumor cell lines showed that cells accumulate in S phase in response to treatment with an active GRO. Analysis of 5-bromodeoxyuridine incorporation by these cells indicated the absence of de novo DNA synthesis, suggesting an arrest of the cell cycle predominantly in S phase. At the same time point, RNA and protein synthesis were found to be ongoing, indicating that arrest of DNA replication is a primary event in GRO-mediated inhibition of proliferation. This specific blockade of DNA replication eventually resulted in altered cell morphology and induction of apoptosis. To characterize further GRO-mediated inhibition of DNA replication, we used an in vitro assay based on replication of SV40 DNA. GROs were found to be capable of inhibiting DNA replication in the in vitro assay, and this activity was correlated to their antiproliferative effects. Furthermore, the effect of GROs on DNA replication in this assay was related to their inhibition of SV40 large T antigen helicase activity. The data presented suggest that the antiproliferative activity of GROs is a direct result of their inhibition of DNA replication, which may result from modulation of a replicative helicase activity.Oligonucleotides can recognize both nucleic acids and proteins with a high degree of specificity. This is a major reason why they have been widely investigated as potential therapeutic agents for cancer, viral infections, and inflammatory diseases. Oligonucleotides can achieve target recognition by sequence-specific interactions with nucleic acids or proteins such as in the antisense, antigene, or decoy approaches (1-4). Alternatively, target recognition can be due to the specific threedimensional structure of an oligonucleotide, as in the aptamer approach (5, 6). These aptameric oligonucleotides often contain secondary structure elements such as hairpins or G-quartets. The formation of G-quartet structures is also thought to contribute to non-antisense growth inhibitory effects of G-rich phosphodiester and phosphorothioate oligonucleotides (7-9).Recently, we reported (9) on a novel class of phosphodiester G-rich oligonucleotides (GROs) 1 that could strongly inhibit the in vitro proliferation of tumor cells derived from prostate, breast, and cervical carcinomas. The antiproliferative GROs were able to form stable secondary structures consistent with G-quartet format...

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Urokinase-induced mitogenesis is mediated by casein kinase 2 and nucleolin

Cited by 84 publications

References 54 publications

An Acidic Peptide Sequence of Nucleolin-Related Protein Can Mediate the Attachment of Calcium Oxalate to Renal Tubule Cells

An Acidic Peptide Sequence of Nucleolin-Related Protein Can Mediate the Attachment of Calcium Oxalate to Renal Tubule Cells

Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Regulation of WNT/β-Catenin Signaling Is Enhanced in Irradiated Medulloblastoma Cells

Inhibition of DNA Replication and Induction of S Phase Cell Cycle Arrest by G-rich Oligonucleotides

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