Nucleophosmin and human cancer

Lim, Mi Jung; Wang, Xin Wei

doi:10.1016/j.cdp.2006.10.008

Cited by 105 publications

(108 citation statements)

References 63 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…Moreover, B23 maintains genomic integrity by controlling DNA repair mechanisms and centrosome duplication during mitosis. It has also emerged as a regulator of the p53/p14ARF/MDM2 pathway, stabilizing p53, thus playing a role in mediating the cellular stress response (35,(37)(38)(39). B23 has been strongly implicated in hematopoietic malignancies, in which translocations and mutations involving the gene have been reported in various lymphomas and leukemias, giving rise to fusion proteins or mutant products (40).…”

Section: Discussionmentioning

confidence: 99%

The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator

Feldman

Roniger

Bar-Sinai

et al. 2012

Molecular Cancer Research

View full text Add to dashboard Cite

Mouse mammary tumor virus (MMTV) is associated primarily with mammary carcinomas and lymphomas. The signal peptide of the MMTV envelope precursor is uniquely targeted to nucleoli of cells that harbor the virus, where it can function as a nuclear export factor for intron-containing transcripts. Antibodies to this signal peptide, which we refer to as p14, were previously shown to label nucleoli in a subset of human breast cancers. To look for additional cellular functions of p14, different mutants were ectopically expressed in the MCF-7 human breast cancer cell line. This approach identified motifs responsible for its nucleolar targeting, nucleocytoplasmic shuttling, target protein (B23, nucleophosmin) binding, and phosphorylation at serine 18 and 65 both in situ and in vitro. To test the role of these phosphorylation sites, we carried out in vivo tumorigenesis studies in severe combined immunodeficient mice. The findings show that the p14-Ser65Ala mutation is associated with impaired tumorigenicity, whereas the p14-Ser18Ala mutation is associated with enhanced tumorigenicity. Microarray analysis suggests that phosphorylation at serine 18 or at serine 65 is associated with transcriptional regulation of the L5 nucleolar ribosomal protein (a p14 target) and the Erb-B signal transduction pathway. Taken together, these results show that the phosphorylation status of p14 determines whether it functions as a pro-oncogenic or antioncogenic modulator.

show abstract

Section: Discussionmentioning

confidence: 99%

The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator

Feldman

Roniger

Bar-Sinai

et al. 2012

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…80 Moreover, phosphorylation of nucleophosmin by casein kinase 2 (CK2) may regulate nucleolus formation and ribosome biogenesis by altering its interaction with other nucleolar components. 78,81 Phosphorylation of Rb also mediates its nucleolar accumulation at the end of S-phase through an interaction with nucleophosmin. 82 Besides phosphorylation, acetylation may also affect partitioning of nucleolar proteins between the nucleolus and the nucleoplasm.…”

Section: The "Plurifunctional" Nucleolus and Tumor Suppressionmentioning

confidence: 99%

Beyond Repair Foci: Subnuclear Domains and the Cellular Response to DNA Damage

Dellaire¹,

Bazett-Jones²

2007

Cell Cycle

View full text Add to dashboard Cite

“…However, the roles of NPM in cell differentiation and the mechanisms of its transportation and relocation are still largely unknown. Recent data suggest NPM is tightly correlated with the development of a tumor (1), its expression level is enhanced in various cancers, such as bladder cancer and prostate cancer (3)(4)(5). As a potential proto-oncogene, NPM can affect cell growth through multiple pathways (1).…”

Section: Introductionmentioning

confidence: 99%

Regulatory role of nucleophosmin during the differentiation of human liver cancer cells

Liu

et al. 2014

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Nucleophosmin (NPM, also known as B23), mainly localized in the nucleolus, has been reported to be overexpressed in many types of human cancer, including colon, ovarian, prostate and gastric cancer. NPM was identified while screening the differential nuclear matrix proteins during HMBA-induced differentiation of human liver cancer cells. We investigated the aberrant expression and subcellular localization of NPM in clinical liver cancer tissues and a cell line with the aim of providing more evidence for revealing the roles of NPM on regulating liver cancer cell proliferation and differentiation. In addition, we studied the potential interaction between NPM and several important proteins. Our results revealed that NPM protein was overexpressed in cancer cells, which was in accordance with the overexpressed mRNA in cancer tissues compared to the corresponding noncancer tissues. We also found a decrease of NPM in protein and mRNA levels upon treatment with the differentiation reagent HMBA. We focused on the aberrant localization of NPM. Immunochemistry and immunofluorescence revealed aberrant cytoplasmic and nucleoplasm localization of NPM in liver cancer tissues and its colocalization with c-Myc, c-Fos, P53 and Rb in the SMMC-7721 cell line. The interactions between NPM and the above proteins were confirmed by GST pull-down assay and co-immunoprecipitation assay. These findings indicate that NPM plays a regulatory role in liver cancer, which deserves in-depth investigation. IntroductionNucleophosmin (NPM) is a ubiquitous nucleolar phosphoprotein with multifunction. NPM has been shown to associate with the assembly and transport of ribosome, the duplication of centrosome and DNA damage response (1,2). NPM regulates the nucleolus activities and cell proliferation, indicating its crucial roles in cell growth. However, the roles of NPM in cell differentiation and the mechanisms of its transportation and relocation are still largely unknown. Recent data suggest NPM is tightly correlated with the development of a tumor (1), its expression level is enhanced in various cancers, such as bladder cancer and prostate cancer (3-5). As a potential proto-oncogene, NPM can affect cell growth through multiple pathways (1). Nevertheless, how NPM affects the reversal of malignant type of tumor cells is still unknown.In our previous study, we found NPM was a nuclear matrix protein and its expression was downregulated in the induced differentiation of human osteosarcoma, human neuroblastoma tumors and human liver cancer (6-8), indicating NPM functioned in regulating the differentiation of tumor cells (9). Liver cancer is the most common malignant gastrointestinal cancer and the screening for functional proteins related to liver tumor cell differentiation will contribute to the elucidation of the mechanism of liver cancer development and its early diagnosis. Hereby, based on the induced effect of hexamethylene bisacetamide (HMBA) on the differentiation of human liver cancer cells, we extended our study to investigate the loca...

show abstract

Nucleophosmin and human cancer

Cited by 105 publications

References 63 publications

The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator

The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator

Beyond Repair Foci: Subnuclear Domains and the Cellular Response to DNA Damage

Regulatory role of nucleophosmin during the differentiation of human liver cancer cells

Contact Info

Product

Resources

About