Nucleophosmin is a component of the fructoselysine-specific receptor in cell membranes of Mono Mac 6 and U937 monocyte-like cells

Brandt, Rowena; Nawka, Mato; Kellermann, Josef; Salazar, Ramona; Becher, Dörte; Krantz, S

doi:10.1016/j.bbagen.2003.11.003

Cited by 14 publications

(5 citation statements)

References 11 publications

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“…It has long been noted that a few of the nucleolar proteins, such as B23 (nucleophosmin), C23 (nucleolin), and Nopp140 can redistribute in the cell membrane, mediating a variety of cellular activities such as cytoskeleton assembly and angiogenesis, which are far removed from the originally described function of these molecules (45)(46)(47)(48)(49)(50). The present study reveals a functional link between membrane distribution of a nucleolar protein and invasive neoplastic potential.…”

Section: Discussionmentioning

confidence: 77%

GSK-3β–Regulated N-Acetyltransferase 10 Is Involved in Colorectal Cancer Invasion

Zhang

Hou

Wang

et al. 2014

Clinical Cancer Research

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Purpose: NAT10 (N-acetyltransferase 10) is a nucleolar protein, but may show subcellular redistribution in colorectal carcinoma. In this study, we evaluated membranous staining of NAT10 in colorectal carcinoma and its clinical implications, and explored the mechanism of regulation of NAT10 redistribution.Experimental Design: The expression and subcellular redistribution of NAT10, b-catenin, E-cadherin, and GSK-3b were evaluated by immunohistochemistry in 222 cases of colorectal carcinoma. Regulation of NAT10 and its influence on cell motility were analyzed with inhibitors of GSK-3b, transfection of wild-type or kinase-inactivated GSK-3b, or expression of various domains of NAT10, and evaluated with immunofluorescence, Western blotting, and Transwell assays.Results: NAT10 localized mainly in the nucleoli of normal tissues, and was redistributed to the membrane in cancer cells, particularly at the invasive "leading edge" of the tumor. This correlated well with nuclear accumulation of b-catenin (P < 0.001; x 2 ¼ 68.213). In addition, NAT10 membrane staining reflected the depth of invasion and tendency to metastasize (all P values < 0.001), and was associated with a poorer prognosis (P ¼ 0.023; x 2 ¼ 5.161). Evaluation of the mechanism involved demonstrated that subcellular redistribution of NAT10 may result from its increased stability and nuclear export, which is brought about by inhibition of GSK-3b. Moreover, redistribution of NAT10 induces alteration of cytoskeletal dynamics and increases cancer cell motility. Conclusion:The subcellular redistribution of NAT10 can be induced by decreases in GSK-3b activity. This redistribution increases cancer cell motility, and is, thus, correlated with invasive potential and poorer clinical outcome. This finding suggests that NAT10 may be a useful prognostic marker and potential therapeutic target in colorectal carcinoma.

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Section: Discussionmentioning

confidence: 77%

GSK-3β–Regulated N-Acetyltransferase 10 Is Involved in Colorectal Cancer Invasion

Zhang

Hou

Wang

et al. 2014

Clinical Cancer Research

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“…NPM is an abundant nuclear protein [ 29 ] that can translocate to the cytoplasm [ 30 ]. Recently, it was found to be localized in the cell membrane and to be a component of the fructose lysine-specific receptor expressed by monocyte-like cell lines [ 31 ]. Thus, NPM could well interact with anionic phospholipids at the cell membrane to form a typical lupus-related immunogenic complex, which could be released.…”

Section: Discussionmentioning

confidence: 99%

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Lartigue

Drouot

Jouen³

et al. 2005

Arthritis Res Ther

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We showed previously that nucleophosmin (NPM), a nucleolar phosphoprotein, is recognized by sera from (NZW × BXSB)F 1 (WB) mice, a model of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome. In the present study we analysed the prevalence and kinetics of anti-NPM autoantibodies in WB mice by a solid-phase ELISA with recombinant human (rh) NPM as the antigen and showed that most male WB mouse sera had anti-NPM antibodies that were responsible for their indirect immunofluorescence staining pattern on Hep-2 cells. Anti-NPM antibodies were significantly associated with anti-cardiolipin (aCL) antibodies. This antibody profile mirrored that observed in certain human SLE sera because anti-NPM antibodies were detected in 28% of the sera from patients with SLE and were similarly associated with aCL antibodies. The demonstration that rhNPM bound to cardiolipin (CL) in vitro and increased the CL-binding activity of a WB-derived aCL monoclonal antibody indicates that NPM can interact with CL to form SLE-related immunogenic particles that might be responsible for the concomitant production of anti-NPM and aCL antibodies.

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“…Although the majority of NPM protein resides in the nucleus, it functions as a molecular shuttle to the cytoplasm and variant forms that result from chromosomal translocations or mutations may be redirected to the cytosol (Grisendi et al, 2006;Falini et al, 2007). There is little insight available regarding the roles of NPM outside of the nucleus, aside from regulation of cell cycle progression by interaction with the centrosome (Okuda et al, 2000), regulation of apoptosis via binding to Bax (Kerr et al, 2006), and functioning as a component of the fructose lysin-specific binding proteins in the plasma membrane (Brandt et al, 2004). In the current study, we identified the physical association of NPM with CXCR4 mutants that assume a conformation that confers autonomous and constitutive G protein activation, suggesting that it may regulate signal transduction.…”

Section: Discussionmentioning

confidence: 99%

Association of Nucleophosmin Negatively Regulates CXCR4-Mediated G Protein Activation and Chemotaxis

et al. 2007

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CXCR4, the primary receptor for CXCL12, plays a critical role in the development of hematopoietic, vascular, central nervous, and immune systems by mediating directional migration of precursor cells. This mechanism promotes homing of tumor cells to metastatic sites that secrete CXCL12, and CXCR4 expression is a negative prognostic factor in acute myelogenous leukemia (AML). To elucidate mechanisms that regulate CXCR4 signaling, we used a proteomic approach to identify proteins physically associated with CXCR4. Analysis of CXCR4 immune complexes identified nucleophosmin (NPM), which was confirmed by reciprocal coimmunoprecipitation for NPM. Constitutively active CXCR4 variants bound higher levels of NPM than the wild-type receptor, which was reversed by T140, an inverse agonist. NPM binding to CXCR4 localized interactions to the C terminus and cytoplasmic loop (CL)-3, but not CL-1 or CL-2. Alanine scanning mutagenesis demonstrated that positively charged amino acids in CL-3 were critical for NPM binding. Recombinant NPM decreased GTP binding in membrane fractions after activation of CXCR4 by CXCL12. Suppression of NPM expression enhanced chemotactic responses to CXCL12, and, conversely, overexpression of a cytosolic NPM mutant reduced chemotaxis induced by CXCL12. This study provides evidence for a novel role for NPM as a negative regulator of CXCR4 signaling induced by CXCL12 that may be relevant to the biology of AML.

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Nucleophosmin is a component of the fructoselysine-specific receptor in cell membranes of Mono Mac 6 and U937 monocyte-like cells

Cited by 14 publications

References 11 publications

GSK-3β–Regulated N-Acetyltransferase 10 Is Involved in Colorectal Cancer Invasion

GSK-3β–Regulated N-Acetyltransferase 10 Is Involved in Colorectal Cancer Invasion

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Association of Nucleophosmin Negatively Regulates CXCR4-Mediated G Protein Activation and Chemotaxis

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