The Experts below are selected from a list of 7635 Experts worldwide ranked by ideXlab platform
Benjamin Yat-ming Yung - One of the best experts on this subject based on the ideXlab platform.
-
Association of Nucleophosmin/B23 with bladder cancer recurrence based on immunohistochemical assessment in clinical samples.
Acta pharmacologica Sinica, 2008Co-Authors: Ke-hung Tsui, Horng-heng Juang, Tsong-hai Lee, Phei-lang Chang, Chien-lun Chen, Benjamin Yat-ming YungAbstract:Aim: To investigate the possible correlation of Nucleophosmin/B23 expression with bladder carcinoma recurrence. Methods: Surgically-resected bladder tumors staged pTa to pT4 were examined for Nucleophosmin/B23 expression by immuno-histochemistry. The study group consisted of 132 consecutive patients surgically treated at Chang Gung Memorial Hospital between December 1998 and November 1999. The mean follow up was 72 months (range: 48-84 months). Results: Nuclear Nucleophosmin/B23 staining was detected in 96% of advanced stage and poorly-differentiated tumors. Higher Nucleophosmin/B23 levels were linked to more advanced tumor stages, grades, poor prognosis, and likelihood of recurrence ( P P =0.009). Conclusion: The results suggest that Nucleophosmin/B23 is a favorable prognostic indicator for bladder cancer. Nucleophosmin/B23 could be a useful molecular tumor marker for predicting bladder cancer recurrence.
-
Oncogenic role of Nucleophosmin/B23.
Chang Gung medical journal, 2007Co-Authors: Benjamin Yat-ming YungAbstract:Nucleophosmin/B23 was first identified as a nucleolar protein expressed at higher levels in cancer cells compared to normal cells. Nucleophosmin/B23 has long been thus thought to have a role in tumor formation. With our efforts and others in the last 15 years, Nucleophosmin/B23 has proven to have an oncogenic role. In this review, we provide evidence suggesting that Nucleophosmin/B23 may be a crucial gene in regulation of cancer growth and discuss how Nucleophosmin/B23 can contribute to tumorigenesis.
-
Ras-dependent recruitment of c-Myc for transcriptional activation of Nucleophosmin/B23 in highly malignant U1 bladder cancer cells.
Molecular pharmacology, 2006Co-Authors: Chun Wei Yeh, Sheng Shun Huang, Ru Ping Lee, Benjamin Yat-ming YungAbstract:U1 bladder cancer cells of high malignancy exhibited higher proliferation capacity than U4 premalignant cells. Higher expression of Ras, c-Myc, and Nucleophosmin/B23 and greater c-Myc transactivation and Nucleophosmin/B23 promoter activities were detected in U1 cells compared with U4 cells. Moreover, c-Myc and Nucleophosmin/B23 were increased in U1 but not in U4 cells upon serum stimulation from quiescence. Likewise, only in U1 cells could serum stimulate transcriptional activity of Nucleophosmin/B23 promoter and c-Myc response element. The increase of Nucleophosmin/B23 promoter activity could be abrogated by mitogen-activated protein kinase/extracellular signal-regulated kinase activating kinase inhibitor and was associated with recruitment of c-Myc to the promoter. U1 cells constitutively expressing dominant-negative Ras reduced the levels of Ras, Nucleophosmin/B23, and p-ERK, and consequently abolished the serum-induced up-regulation of Nucleophosmin/B23 promoter activity and c-Myc promoter recruitment. Our results indicate that Ras and c-Myc play important roles in the up-regulation of Nucleophosmin/B23 during proliferation of cells associated with a high degree of malignancy, thus outlining a signaling cascade involving these factors in the cancer cells.
-
Nucleophosmin/B23 regulates transcriptional activation of E2F1 via modulating the promoter binding of NF-κB, E2F1 and prB
Cellular signalling, 2006Co-Authors: Chiao Yun Lin, Yu Chun Liang, Benjamin Yat-ming YungAbstract:Expression of Nucleophosmin/B23 and E2F1 and E2F1-dependent transcription increased in U1 bladder cancer cells upon serum stimulation from quiescence. Nucleophosmin/B23-siRNA treatment abrogated such increase of E2F1-dependent transcriptional activity. In identifying physiologically important factors that may occupy E2F1 promoter and regulate its activity in vivo, we found that the pattern of NF-kappaB, E2F1 and pRB recruitment to E2F1 promoter changed in a strikingly dynamic fashion as cells progressed from quiescence into serum-stimulated growth. E2F1 promoter activity in quiescent cells was associated with recruitment of NF-kappaB. NF-kappaB was replaced largely by E2F1 in concert with gene activation during the early stage (12 h) of serum stimulation. At late stage (24 h) of serum stimulation, pRB was then recruited to the E2F1-promoter complex to counterbalance its activity. Upon siRNA-mediated reduction of intracellular Nucleophosmin/B23, E2F1 and pRB were recruited to the promoter with the dissociation of NF-kappaB concomitant with gene inactivation. Based on immunoprecipitation experiments, Nucleophosmin/B23 was found to be associated with NF-kappaB in cells grown in serum-supplemented but not in serum-deprived medium. Furthermore, Nucleophosmin/B23 could also be co-immunoprecipitated with ppRB at the early stage (12 h) but not at the late stage (24 h) of serum stimulation. The results demonstrate a novel mechanism for transcriptional regulation of E2F1 and identify the functional role of Nucleophosmin/B23 in modulating the binding of NF-kappaB, E2F1 and pRB to activate E2F1 promoter.
-
Nucleophosmin/B23 regulates PCNA promoter through YY1.
Biochemical and biophysical research communications, 2005Co-Authors: Jing J. Weng, Benjamin Yat-ming YungAbstract:Ectopic over-expression of Nucleophosmin/B23 caused a marked up-regulation in the amounts of Yin Yang 1 (YY1) and proliferating cellular nuclear antigen (PCNA) proteins. Transfection with Nucleophosmin/B23-targeting siRNA induced a decrease in the intracellular amounts of Nucleophosmin/B23, YY1, and PCNA. PCNA expression and its promoter activity were attenuated either by Nucleophosmin/B23-siRNA or YY1-siRNA. The ChIP assay showed that positive regulation of PCNA is achieved by binding of YY1 to the initiation site of PCNA promoter. The binding of YY1 to the PCNA promoter and histone H4 acetylation was significantly decreased in Nucleophosmin/B23-siRNA-treated cells as compared to control vector-transfected cells. Mutation in YY1 binding site resulted in the loss of PCNA promoter activity and the binding of YY1 to the promoter. The results have indicated that YY1 binds to the initiation site of the PCNA promoter along with histone H4 acetylation, leading to transcriptional activity. We have demonstrated that Nucleophosmin/B23 plays an important role in the regulation of PCNA through YY1.
Wen H. Liu - One of the best experts on this subject based on the ideXlab platform.
-
Nucleophosmin/B23 regulates the susceptibility of human leukemia HL-60 cells to sodium butyrate-induced apoptosis and inhibition of telomerase activity.
International journal of cancer, 1999Co-Authors: Wen H. Liu, Chen Y. Hsu, Benjamin Yat-ming YungAbstract:Stable clones of HL-60 cells in which Nucleophosmin/B23 was over-expressed or down-regulated were established. The Nucleophosmin/B23 protein levels in Nucleophosmin/B23 over-expressed (pCR3-B23) or down-regulated (pCR3-32B) cells during BuONa/vanadate-induced apoptosis were characterized as compared with control vector-transfected (pCR3) cells. Over-expression of Nucleophosmin/B23 resulted in decreased susceptibility of the cells to BuONa/vanadate-induced apoptosis. The response to inhibition of telomerase activity under BuONa/vanadate treatment also decreased in Nucleophosmin/B23 over-expressed (pCR3-B23) cells. On the other hand, down-regulation of Nucleophosmin/B23 made the cells more susceptible to BuONa-induced apoptosis or inhibition of telomerase activity. More precisely, by serial dilutions of each extract, the telomerase activity of the cells without drug treatment was determined and was found to be higher in Nucleophosmin/B23 over-expressed (pCR3-B23) cells and lower in Nucleophosmin/B23 down-regulated (pCR3-32B) cells as compared with the control vector-transfected (pCR3) cells. Our results indicate that Nucleophosmin/B23 plays a functional role in the control of cellular apoptosis and immortalization.
-
Berberine-induced apoptosis of human leukemia HL-60 cells is associated with down-regulation of Nucleophosmin/B23 and telomerase activity.
International journal of cancer, 1999Co-Authors: Chen Y. Hsu, Wen H. Liu, Benjamin Yat-ming YungAbstract:The steady-state level of Nucleophosmin/B23 mRNA decreased during berberine-induced (25μg/ml, 24 to 96 hr) apoptosis of human leukemia HL-60 cells. A decline in telomerase activity was also observed in HL-60 cells treated with berberine. A stable clone of Nucleophosmin/B23 over-expressed in HL-60 cells was selected and found to be less responsive to berberine-induced apoptosis. About 35% to 63% of control vector–transfected cells (pCR3) exhibited morphological characteristics of apoptosis, while about 8% to 45% of Nucleophosmin/B23-over-expressed cells (pCR3-B23) became apoptotic after incubation with 15μg/ml berberine for 48 to 96 hr. DNA extracted from pCR3 cells contained more fragmented DNA than pCR3-B23 cells during treatment with 15μg/ml berberine for 24 to 48 hr. Our results indicate that berberine-induced apoptosis is associated with down-regulation of Nucleophosmin/B23 and telomerase activity. We also suggest that Nucleophosmin/B23 may play an important role in the control of the cellular response to apoptosis induction. Int. J. Cancer81:923–929, 1999. © 1999 Wiley-Liss, Inc.
-
Mortalization of human promyelocytic leukemia HL-60 cells to be more susceptible to sodium butyrate-induced apoptosis and inhibition of telomerase activity by down-regulation of Nucleophosmin/B23.
Oncogene, 1998Co-Authors: Wen H. Liu, Benjamin Ym YungAbstract:Vanadate (10 μM), a potent inhibitor of tyrosine phosphatase, added simultaneously potentiated BuONa-induced (1 mM) apoptosis. The steady-state level of Nucleophosmin/B23 mRNA and the total cellular Nucleophosmin/B23 protein decreased during the BuONa/vanadate-induced apoptosis. Stabilization and promotor transcriptional activity assays indicate that the decrease in Nucleophosmin/B23 mRNA in BuONa/vanadate-treated HL-60 cells was transcriptionally regulated. A decline in telomerase activity was observed in HL-60 cells treated with BuONa/vanadate for 24–96 h. There was virtually no decline of Nucleophosmin/B23 mRNA nor the telomerase activities during the growth arrest by serum-starvation. The decrease in Nucleophosmin/B23 mRNA expression and telomerase activity in HL-60 cells subsequent to BuONa/vanadate treatment can thus be attributed to cellular apoptosis rather than the growth arrest induced by BuONa/vanadate. Nucleophosmin/B23 antisense oligomer treatment significantly potentiated BuONa-induced apoptosis and inhibition of telomerase activity. Results of this study suggest that Nucleophosmin/B23 is one of the key elements in the down-regulation of nucleolar function for cellular apoptosis and mortalization.
Mary Dasso - One of the best experts on this subject based on the ideXlab platform.
-
Nucleolar protein B23/Nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases.
The Journal of cell biology, 2008Co-Authors: Chawon Yun, Yonggang Wang, Debaditya Mukhopadhyay, Peter S. Backlund, Nagamalleswari Kolli, Alfred L. Yergey, Keith D. Wilkinson, Mary DassoAbstract:Ubiquitin-like protein/sentrin-specific proteases (Ulp/SENPs) mediate both processing and deconjugation of small ubiquitin-like modifier proteins (SUMOs). Here, we show that Ulp/SENP family members SENP3 and SENP5 localize within the granular component of the nucleolus, a subnucleolar compartment that contains B23/Nucleophosmin. B23/Nucleophosmin is an abundant shuttling phosphoprotein, which plays important roles in ribosome biogenesis and which has been strongly implicated in hematopoietic malignancies. Moreover, we found that B23/Nucleophosmin binds SENP3 and SENP5 in Xenopus laevis egg extracts and that it is essential for stable accumulation of SENP3 and SENP5 in mammalian tissue culture cells. After either codepletion of SENP3 and SENP5 or depletion of B23/Nucleophosmin, we observed accumulation of SUMO proteins within nucleoli. Finally, depletion of these Ulp/SENPs causes defects in ribosome biogenesis reminiscent of phenotypes observed in the absence of B23/Nucleophosmin. Together, these results suggest that regulation of SUMO deconjugation may be a major facet of B23/Nucleophosmin function in vivo.
-
nucleolar protein b23 Nucleophosmin regulates the vertebrate sumo pathway through senp3 and senp5 proteases
Journal of Cell Biology, 2008Co-Authors: Chawon Yun, Yonggang Wang, Debaditya Mukhopadhyay, Peter S. Backlund, Nagamalleswari Kolli, Alfred L. Yergey, Keith D. Wilkinson, Mary DassoAbstract:Ubiquitin-like protein/sentrin-specific proteases (Ulp/SENPs) mediate both processing and deconjugation of small ubiquitin-like modifier proteins (SUMOs). Here, we show that Ulp/SENP family members SENP3 and SENP5 localize within the granular component of the nucleolus, a subnucleolar compartment that contains B23/Nucleophosmin. B23/Nucleophosmin is an abundant shuttling phosphoprotein, which plays important roles in ribosome biogenesis and which has been strongly implicated in hematopoietic malignancies. Moreover, we found that B23/Nucleophosmin binds SENP3 and SENP5 in Xenopus laevis egg extracts and that it is essential for stable accumulation of SENP3 and SENP5 in mammalian tissue culture cells. After either codepletion of SENP3 and SENP5 or depletion of B23/Nucleophosmin, we observed accumulation of SUMO proteins within nucleoli. Finally, depletion of these Ulp/SENPs causes defects in ribosome biogenesis reminiscent of phenotypes observed in the absence of B23/Nucleophosmin. Together, these results suggest that regulation of SUMO deconjugation may be a major facet of B23/Nucleophosmin function in vivo.
Brunangelo Falini - One of the best experts on this subject based on the ideXlab platform.
-
Altered Nucleophosmin transport in acute myeloid leukaemia with mutated NPM1: molecular basis and clinical implications
Leukemia, 2009Co-Authors: Brunangelo Falini, Arcangelo Liso, Stefano Pileri, N Bolli, M P Martelli, R Mannucci, I NicolettiAbstract:Nucleophosmin ( NPM1 ) is a highly conserved nucleo-cytoplasmic shuttling protein that shows a restricted nucleolar localization. Mutations of NPM1 gene leading to aberrant cytoplasmic dislocation of Nucleophosmin (NPMc+) occurs in about one third of acute myeloid leukaemia (AML) patients that exhibit distinctive biological and clinical features. We discuss the latest advances in the molecular basis of Nucleophosmin traffic under physiological conditions, describe the molecular abnormalities underlying altered transport of Nucleophosmin in NPM1 -mutated AML and present evidences supporting the view that cytoplasmic Nucleophosmin is a critical event for leukaemogenesis. We then outline how a highly specific immunohistochemical assay can be exploited to diagnose NPM1 -mutated AML and myeloid sarcoma in paraffin-embedded samples by looking at aberrant Nucleophosmin accumulation in cytoplasm of leukaemic cells. This procedure is also suitable for detection of haemopoietic multilineage involvement in bone marrow trephines. Moreover, use of immunohistochemistry as surrogate for molecular analysis can serve as first-line screening in AML and should facilitate implementation of the 2008 World Health Organization classification of myeloid neoplasms that now incorporates AML with mutated NPM1 (synonym: NPMc+ AML) as a new provisional entity. Finally, we discuss the future therapeutic perspectives aimed at reversing the altered Nucleophosmin transport in AML with mutated NPM1 .
-
Cytoplasmic Nucleophosmin is not detected in blastic plasmacytoid dendritic cell neoplasm.
Haematologica, 2008Co-Authors: Fabio Facchetti, Maria Paola Martelli, Stefano Pileri, Claudio Agostinelli, Marco Paulli, Adriano Venditti, Massimo F. Martelli, Brunangelo FaliniAbstract:Acute myeloid leukemia carrying cytoplasmic mutated Nucleophosmin (NPMc+ AML) and blastic plasmacytoid dendritic cell neoplasm have been included as new entities in the 4th edition (2008) WHO classification of myeloid neoplasms. These conditions may show clinical and pathological overlapping features (leukemic and skin involvement, and expression of macrophage markers). In this study, we provide evidence that aberrant cytoplasmic dislocation of Nucleophosmin – the immunohistochemical surrogate for NPM1 mutations – allows the two entities to be genetically separated. In fact, Nucleophosmin is consistently cytoplasmic in NPMc+ AML (because of the presence of NPM1 mutations), whilst it is nucleus-restricted (predictive of a germline NPM1 gene) in blastic plasmacytoid dendritic cell neoplasm. Our results clearly point cytoplasmic Nucleophosmin (a full predictor of NPM1 mutations) as a new marker for distinguishing NPMc+ AML and blastic plasmacytoid dendritic cell neoplasm, further clarify the cell of origin of NPMc+ AML, and justify the inclusion of these pathological conditions as separate entities in the new WHO classification.
-
npm1 mutations and cytoplasmic Nucleophosmin are mutually exclusive of recurrent genetic abnormalities a comparative analysis of 2562 patients with acute myeloid leukemia
Haematologica, 2008Co-Authors: Brunangelo Falini, Maria Paola Martelli, Cristina Mecucci, Giuseppe Saglio, Francesco Lo Coco, Daniela Diverio, Patrick A Brown, Fabrizio Pane, Marco Mancini, Stefano PileriAbstract:Acute myeloid leukemia carrying NPM1 mutations and cytoplasmic Nucleophosmin (NPMc+ acute myeloid leukemia) represents one-third of adult AML (50–60% of all acute myeloid leukemia with normal karyotype) and shows distinct biological, pathological and clinical features. We confirm in 2562 patients with acute myeloid leukemia our previous observation that NPM1 mutations and cytoplasmic Nucleophosmin are mutually exclusive of recurrent genetic abnormalities. Taken together, these findings make NPMc+ acute myeloid leukemia a good candidate for inclusion in the upcoming World Health Organization classification.
-
In human genome, generation of a nuclear export signal through duplication appears unique to Nucleophosmin (NPM1) mutations and is restricted to AML.
Leukemia, 2007Co-Authors: Arcangelo Liso, Alessandro Bogliolo, Valerio Freschi, Maria Paola Martelli, Stefano Pileri, M Santodirocco, Niccolo Bolli, M. F. Martelli, Brunangelo FaliniAbstract:In human genome, generation of a nuclear export signal through duplication appears unique to Nucleophosmin ( NPM1 ) mutations and is restricted to AML
-
Nucleophosmin leukaemic mutants contain C-terminus peptides that bind HLA class I molecules.
Leukemia, 2007Co-Authors: Arcangelo Liso, Maria Paola Martelli, Didier Colau, Rim Benmaamar, A. De Groot, W. Martin, Roberta Benedetti, Giorgina Specchia, Pierre Coulie, Brunangelo FaliniAbstract:Nucleophosmin leukaemic mutants contain C-terminus peptides that bind HLA class I molecules
Martin Eilers - One of the best experts on this subject based on the ideXlab platform.
-
A ribosomal protein L23-Nucleophosmin circuit coordinates Miz1 function with cell growth
Nature Cell Biology, 2008Co-Authors: Michael Wanzel, Annika C. Russ, Daniela Kleine-kohlbrecher, Emanuela Colombo, Pier-guiseppe Pelicci, Martin EilersAbstract:Miz1, a Myc-associated transcriptional repressor inhibits cell proliferation. Eilers and colleagues show that the ribosomal protein L23 negatively regulates Miz1 by retaining its activator, Nucleophosmin, in the nucleolus. The Myc-associated zinc-finger protein, Miz1, is a negative regulator of cell proliferation and induces expression of the cell-cycle inhibitors p15^Ink4b and p21^Cip1. Here we identify the ribosomal protein L23 as a negative regulator of Miz1-dependent transactivation. L23 exerts this function by retaining Nucleophosmin, an essential co-activator of Miz1 required for Miz1-induced cell-cycle arrest, in the nucleolus. Mutant forms of Nucleophosmin found in acute myeloid leukaemia fail to co-activate Miz1 and re-localize it to the cytosol. As L23 is encoded by a direct target gene of Myc, this regulatory circuit may provide a feedback mechanism that links translation of Myc target genes and cell growth to Miz1-dependent cell-cycle arrest.
-
A ribosomal protein L23-Nucleophosmin circuit coordinates Miz1 function with cell growth
Nature cell biology, 2008Co-Authors: Michael Wanzel, Annika C. Russ, Daniela Kleine-kohlbrecher, Emanuela Colombo, Pier-guiseppe Pelicci, Martin EilersAbstract:The Myc-associated zinc-finger protein, Miz1, is a negative regulator of cell proliferation and induces expression of the cell-cycle inhibitors p15(Ink4b) and p21(Cip1). Here we identify the ribosomal protein L23 as a negative regulator of Miz1-dependent transactivation. L23 exerts this function by retaining Nucleophosmin, an essential co-activator of Miz1 required for Miz1-induced cell-cycle arrest, in the nucleolus. Mutant forms of Nucleophosmin found in acute myeloid leukaemia fail to co-activate Miz1 and re-localize it to the cytosol. As L23 is encoded by a direct target gene of Myc, this regulatory circuit may provide a feedback mechanism that links translation of Myc target genes and cell growth to Miz1-dependent cell-cycle arrest.
