The expression of the nuclear matrix proteins NuMA, topoisomerase II-α, and -β in bone and osseous cell culture: regulation by parathyroid hormone

Feister, Hilary A.; Onyia, Jude E.; Miles, Rebecca R.; Yang, Xiaonan; Galvin, Rachelle J. Sells; Hock, Janet M.; Bidwell, Joseph P.

doi:10.1016/s8756-3282(99)00269-0

Cited by 21 publications

(15 citation statements)

References 46 publications

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“…A: Schematic representation of isoform GFP-11H, its truncated derivatives, isoforms 13H, 21H, and 28H, and degree of association with the UMR-106 nuclear matrix following in situ sequential extraction. The only constructs to exhibit association with the nuclear matrix were the GFP-11H full-length construct [1-579aa] [Feister et al, 2000;Torrungruang et al, 1998]. Although fluorescent images indicate that NuMA and isoforms 11H and 13H are diffusely distributed throughout the nucleus and excluded from the nucleolus, pseudocolor overlay images reveal that there are regions of non-overlap between these proteins.…”

Section: Discussionmentioning

confidence: 99%

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NP/NMP4 transcription factors have distinct osteoblast nuclear matrix subdomains

et al. 2000

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The mechanisms underlying the coupling of type I collagen and matrix metalloproteinase (MMP) expression to cell structure and adhesion are poorly understood. We propose that nuclear matrix architectural transcription factors link cell structure and transcription via their association with nuclear matrix subdomains and by their capacity for altering promoter geometry. NP/NMP4 are nuclear matrix proteins that contain from five to eight Cys(2)His(2) zinc fingers. Some NP/NMP4 isoforms bind to the rat type I collagen alpha1(I) polypeptide chain promoter in the manner of architectural transcription factors and alter basal transcription in osteoblast-like cells (Thunyakitpisal et al. in review). Certain isoforms of NP/NMP4 are identical to CIZ, Cas-interacting zinc finger protein, a nucleocytoplasmic shuttling protein that associates with focal adhesions and regulates MMP expression [Nakamoto et al. (2000): Mol Cell Biol 20:1649-1658]. To better understand the role of subnuclear architecture in collagen and MMP expression, we mapped the osteoblast nuclear distribution of NP/NMP4 proteins and identified the functional motifs necessary for nuclear localization and nuclear matrix targeting. Immunofluorescence microscopy was used to determine the cellular and subnuclear distribution of native NP/NMP4 proteins and green fluorescent protein (GFP)-NP/NMP4 fusion proteins in osteoblast-like cells. All GFP-NP/NMP4 fusion proteins localized to the nucleus, but accumulated in distinct nuclear matrix subdomains. The zinc finger domain was necessary and sufficient for nuclear import and matrix targeting. We conclude that the arrangement of the NP/NMP4 zinc fingers largely determines the subnuclear location of these isoforms.

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Section: Discussionmentioning

confidence: 99%

“…1E). NuMA is a component of the spindle pole apparatus in dividing cells and comprises the nuclear substructure of some non-dividing cells, including osteoblasts [Feister et al, 2000;Torrungruang et al, 1998]. …”

Section: Np/nmp4 Localizes To Both the Cytosol And Nucleus Of Osteoblmentioning

confidence: 99%

NP/NMP4 transcription factors have distinct osteoblast nuclear matrix subdomains

et al. 2000

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“…To go further and understand the broader role of topoisomerases in osteosarcoma, we did not limit our study to topoisomerase IIα, but we extended the analyses to the three main types of DNA topoisomerases. These enzymes seem to play an essential and cooperative role in nuclear DNA topology and are expressed in normal osteoblasts where their presence is specific of proliferating cells [6,7]. Indeed, whereas the loss of normal osteoblast proliferation correlates with the downregulation of topoisomerase IIα expression, the isoform topoisomerase IIβ is upregulated when osteoblasts have plateaued in growth [6,8].…”

Section: Introductionmentioning

confidence: 99%

Role of Topoisomerases in Pediatric High Grade Osteosarcomas: TOP2A Gene Is One of the Unique Molecular Biomarkers of Chemoresponse

Nguyen

Lasthaus

Guérin

et al. 2013

Cancers

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Currently, the treatment of pediatric high-grade osteosarcomas systematically includes one topoisomerase IIα inhibitor. This chemotherapy is usually adapted to the response to the neo-adjuvant therapy after surgery. The current and unique marker of chemoresponsiveness is the percentage of viable residual cells in the surgical resection. This late patient management marker has to be evaluated earlier in the therapeutic history of the patients on initial biopsy. Therefore, new biomarkers, especially those involved in the topoisomerase IIα inhibitor response might be good candidates. Therefore, our study was designed to target TOP1, TOP2A and TOP2B genes in 105 fresh-frozen diagnostic biopsies by allelotyping and real-time quantitative PCR. Our analyses in those pediatric osteosarcomas, homogeneously treated, highlighted the frequent involvement of topo-isomerase genes. The main and most important observation was the statistical link between the presence of TOP2A amplification and the good response to neo-adjuvant chemotherapy. Compared to adult cancers, the 17q21 amplicon, including TOP2A and ERBB2 genes, seems to be differentially implicated in the osteosarcoma chemoresponsiveness. Surprisingly, there is no ERBB2 gene co-amplification and the patients harboring TOP2A amplification tend to show a worse survival, so TOP2A analyses remain a preliminary, but a good molecular approach for the evaluation at diagnosis of pediatric osteosarcoma chemoresponsiveness.

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“…Consequently, we sought to probe the nuclear structure and organization using an alternative approach-high content imaging of nuclear mitotic apparatus protein (NuMA) as a test case, since NuMA has been reported as a nuclear matrix protein, the expression and spatial organization of which changes as cells differentiate. 16,17,38,41,42 Similar to the analysis of actin-associated protein gene expression, we assessed the variability in expression of NuMA organization and cell cycle control genes between media conditions via principal component analysis (Fig. 3C).…”

Section: Resultsmentioning

confidence: 99%

“…NuMA is an abundant 240 kD protein that is present in the nucleus of interphase cells and concentrates in the polar regions of the spindle apparatus during mitosis. 41,42,45 As a mitotic-associated protein, NuMA is more closely related to cell cycle progression and thus NuMA organization could be conceivably linked to differential growth kinetics. However, NuMA also functions as a structural protein interface between the nucleoskeleton and RNA splicing.…”

Section: Resultsmentioning

confidence: 99%

Parsing the early cytoskeletal and nuclear organizational cues that demarcate stem cell lineages

Liu¹,

Gordonov²,

Treiser³

et al. 2010

Cell Cycle

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O ur recent report suggests that subtle changes in early cytoskeletal protein-level organization correlate with long-term stem cell lineage commitment. 1 In this extra-view, we dissect changes in the expression of both cytoskeletal and nuclear-regulating genes that may precede and, possibly, govern the formative lineage-specific organizational cues. Human mesenchymal stem cells cultured on glass under basal, osteogenic and adipogenic induction media were analyzed for gene expression profiles within the first 24 hours. Several key actin organization regulating genes and nuclear and cell cycle regulatory genes were found to be upregulated in osteogenic media compared to adipogenic and basal conditions. Given the role of both cytoskeletal and nuclear genes, we examined the possibility of classifying stem cell subpopulations using high content imaging approaches based on the organization of both actin, as previously proposed, as well as nuclear organization and distribution of a nuclear organizational protein, the nuclear mitotic apparatus (NuMA). A pool of combined cytoskeletal and nuclear descriptors were merged into a composite feature space via dimension reduction, data fusion and classification methodologies. This composite approach enabled feature-based identification of specific lineage committed as well as non-differentiating cell populations. Using the improved classification of this high-content imagingbased profiling tool, we demonstrate that MSCs induced to differentiate to either Parsing the early cytoskeletal and nuclear organizational cues that demarcate stem cell lineages

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The expression of the nuclear matrix proteins NuMA, topoisomerase II-α, and -β in bone and osseous cell culture: regulation by parathyroid hormone

Cited by 21 publications

References 46 publications

NP/NMP4 transcription factors have distinct osteoblast nuclear matrix subdomains

NP/NMP4 transcription factors have distinct osteoblast nuclear matrix subdomains

Role of Topoisomerases in Pediatric High Grade Osteosarcomas: TOP2A Gene Is One of the Unique Molecular Biomarkers of Chemoresponse

Parsing the early cytoskeletal and nuclear organizational cues that demarcate stem cell lineages

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