Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nuclear Matrix”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources
PubMed1989

The effect of triiodothyronine on the association of the rat apolipoprotein A-I, C-III and A-IV genes with the nuclear matrix.

The association of apolipoprotein genes with the nuclear matrix of rat liver has been studied. The proportion of the apolipoprotein (apo) A-I, A-IV, C-III and E genes and the albumin gene associated with the matrix in normal rat liver was approximately 11%. In hypothyroid rats, the association of the apo A-I and apo A-IV genes with the matrix was reduced to 1.3% and 2.1% respectively, while in hyperthyroid rats, the association increased to 59% and 39% respectively. In contrast, the association of the apo C-III gene, which is located between the A-I and A-IV genes on chromosome 11, was not significantly affected by thyroid status. The association of the apo E and albumin genes with the matrix was also unaltered by changes in thyroid status. The increased association of the apo A-I and A-IV genes with the nuclear matrix of hyperthyroid animals accompanies the transcriptional activation of these genes by thyroid hormones.

Albumins↗
PubMed1995

Nuclear matrix isolated from plant cells.

Residual nuclear matrices can be successfully obtained from isolated nuclei of different monocot and dicot plant species using either high ionic or low ionic extraction protocols. The protein composition of isolated nuclear matrices depends on the details of isolation protocols. They are stable and present in all cases, a tripartite organization with a lamina, nucleolar matrix, and internal matrix network, and also maintain some of the basic architectural features of intact nuclei. In situ preparations demonstrate the continuity between the nuclear matrix and the plant cytoskeleton. Two-dimensional separation of isolated plant nuclear matrix proteins reveals a heterogeneous polypeptide composition corresponding rather to a complex multicomponent matrix than to a simple nucleoskeletal structure. Immunological identification of some plant nuclear matrix components such as A and B type lamins, topoisomerase II, and some components of the transcription and splicing machineries, internal intermediate filament proteins, and also specific nucleolar proteins like fibrillarin and nucleolin, which associate to specific matrix domains, establish a model of organization for the plant nuclear matrix similar to that of other eukaryotes. Components of the transcription, processing, and DNA-anchoring complexes are associated with a very stable nucleoskeleton. The plant matrix-attached regions share structural and functional characteristics with those of insects, vertebrates, and yeast, and some of them are active in animal cells. In conclusion, the available data support the view that the plant nuclear matrix is basically similar in animal and plant systems, and has been evolutionarily conserved in eukaryotes.

Base Sequence↗
PubMed2001

Cloning and functional analysis of a family of nuclear matrix transcription factors (NP/NMP4) that regulate type I collagen expression in osteoblasts.

Collagen expression is coupled to cell structure in connective tissue. We propose that nuclear matrix architectural transcription factors link cell shape with collagen promoter geometry and activity. We previously indicated that nuclear matrix proteins (NP/NMP4) interact with the rat type I collagen alpha1(I) polypeptide chain (COL1A1) promoter at two poly(dT) sequences (sites A and B) and bend the DNA. Here, our objective was to determine whether NP/NMP4-COL1A1 binding influences promoter activity and to clone NP/NMP4. Promoter-reporter constructs containing 3.5 kilobases (kb) of COL1A1 5' flanking sequence were fused to a reporter gene. Mutation of site A or site B increased promoter activity in rat UMR-106 osteoblast-like cells. Several full-length complementary DNAs (cDNAs) were isolated from an expression library using site B as a probe. These clones expressed proteins with molecular weights and COLIA1 binding activity similar to NP/NMP4. Antibodies to these proteins disrupted native NP/NMP4-COL1A1 binding activity. Overexpression of specific clones in UMR-106 cells repressed COL1A1 promoter activity. The isolated cDNAs encode isoforms of Cys2His2 zinc finger proteins that contain an AT-hook, a motif found in architectural transcription factors. Some of these isoforms recently have been identified as Cas-interacting zinc finger proteins (CIZ) that localize to fibroblast focal adhesions and enhance metalloproteinase gene expression. We observed NP/NMP4/CIZ expression in osteocytes, osteoblasts, and chondrocytes in rat bone. We conclude that NP/NMP4/CIZ is a novel family of nuclear matrix transcription factors that may be part of a general mechanical pathway that couples cell structure and function during extracellular matrix remodeling.

Alternative Splicing↗
PubMed2003

A novel alpha-helical protein, specific to and highly conserved in plants, is associated with the nuclear matrix fraction.

A cDNA for a novel plant protein was isolated from tomato. Nuclear Matrix Protein 1 (NMP1) is a ubiquitously expressed 36 kDa protein, which has no homologues in animals and fungi, but is highly conserved among flowering and non-flowering plants, including gymnosperms, moss, and the liverwort Marchantia polymorpha. NMP1 is predominantly alpha-helical with multiple stretches of short amphipathic regions. Cell fractionation, immunofluorescence, and GFP localization experiments showed that NMP1 is located both in the cytoplasm and nucleus and that the nuclear fraction is associated with the nuclear matrix. NMP1 is a candidate for a plant-specific structural protein with a function both in the nucleus and cytoplasm.

Amino Acid Sequence↗
PubMed2001

p53 binds the nuclear matrix in normal cells: binding involves the proline-rich domain of p53 and increases following genotoxic stress.

The tumour suppressor p53 is a multifunctional protein important for the maintenance of genomic integrity. It is able to form molecular complexes with different DNA targets and also with cellular proteins involved in DNA transcription and DNA repair. In mammalian cells the biochemical processing of DNA occurs on a nuclear sub-structure termed the nuclear matrix. Previously Deppert and co-workers have identified p53 in association with the nuclear matrix in viral- and non-viral transformed cell lines. In the present study we demonstrate, for the first time, that p53 is bound to the nuclear matrix in primary cultures of normal mammalian cells and that this binding increases following DNA damage. Analysis of cell lines expressing structural mutants of p53 revealed that association with the nuclear matrix is independent of the tertiary and quaternary structure of p53. However, the proline-rich domain towards the N-terminus of p53 (residues 67 to 98) appeared important for binding to the nuclear matrix. This was demonstrated by TET-ON regulated expression of p53-derived constructs in p53(-/-) murine embryonic fibroblasts (MEF p53(-/-)). The proline-rich domain of p53 has potential for SH3 protein-protein interaction, and has a role in p53-mediated apoptosis and possibly base excision repair of DNA damage. We discuss our observations in relation to the ability of p53 to facilitate DNA repair and also review evidence indicating that matrix-bound p53 in SV40-transformed cells may facilitate the transforming potential of SV40 large T antigen.

Animals↗
PubMed1999

Altered association of transcriptionally active DNA with the nuclear-matrix after heat shock.

PURPOSE: Exposure of human cells to heat leads to denaturation and aggregation of proteins. Within the nucleus, it has been suggested that protein aggregation is linked to the selective inhibition by hyperthermia of nucleotide excision repair in transcriptionally active genes. In this study it was investigated in detail whether and how the inhibition of repair of transcriptionally active genes might be related to alterations in their association with the nuclear-matrix. MATERIAL AND METHODS: Different protocols for nuclear-matrix isolation (high salt and lithium 3',5'-diiodosalycilate [LIS] extraction of nuclei) were used to compare DNA loop organization and positioning of transcriptionally active genes in both heated and non-heated cells. RESULTS: DNaseI digestion of total genomic DNA in Cu2+ -stabilized LIS-extracted nuclei revealed that heat shock perturbed the formation of nuclear-matrix attachment sites. Specific labelling of active genes indicated that the number of nuclear-matrix attachment sites in transcriptionally active DNA was increased due to the heat shock. At the level of individual genes, heat treatment led to stabilization of the 5' matrix attachment site (MAR) in the transcriptionally active adenosine deaminase (ADA) housekeeping gene. Moreover, heat shock resulted in the formation of an additional MAR at the 3' end of the ADA gene. The inactive 754 locus was unassociated, irrespective of a heat shock. CONCLUSIONS: The reported changes in chromatin structure might underlie the selective inhibition of repair in transcriptionally active genes and consequently may be mechanistically linked to the sensitization of heated cells to ionizing radiation.

Adenosine Deaminase↗
PubMed1994

Characterisation of two intronic nuclear-matrix-attachment regions in the human DNA topoisomerase I gene.

We identify two high-affinity matrix-attachment regions (MAR elements) located in two introns of the human DNA topoisomerase I gene (TOP1). These intronic MAR elements, designated MI and MII, are specifically bound by the nuclear matrix and partition with scaffolds in vitro. One of these MAR elements, MII, is part of a genomic region which is hypersensitive for endogenous nucleases. We have sequenced both DNA elements and have characterized their mode of binding to the nuclear matrix. Experiments with the minor-groove-binding ligands distamycin and chromomycin indicate that the A+T-rich regions, most likely homopolymeric A tracts, are responsible for binding of these DNA elements to the nuclear matrix. MII contains an alu-like element and a segment of curved DNA. Analysis of subfragments of MII show that the curved DNA region itself shows only weak nuclear-matrix binding, and that the high-affinity binding sites are located on subfragments on the 5' side of the curved DNA. In addition, we found that the alu-like sequence does not contribute significantly to the binding of MII and of subfragments of MII to nuclear-matrix proteins. Comparing the distribution of repetitive sequences in the cloned parts of human DNA topoisomerase I gene with the location of high-affinity matrix-binding sites we find no evidence that repetitive DNA may be located close to MAR elements as has been previously suggested.

Binding Sites↗
PubMed2000

Interaction of exogenous DNA with the nuclear matrix of live spermatozoa.

Sperm chromatin is a highly organized array of protamines and DNA, with the protamines serving to tightly condense the DNA into a compact, defined structure. We have previously demonstrated that the sperm nucleus is an ordered library of DNA organized into functional zones, such as the nuclear matrix and nuclear annulus. Other laboratories have suggested that mouse spermatozoa can interact with exogenous pSV2CAT plasmid DNA. In this work, we explored this interaction and examined the subcellular localization of the exogenous DNA. We found a repeatable association of exogenous DNA with a specific region of the sperm nuclear matrix. This region of the nucleus correlates with the equatorial segment of the sperm head. This interaction requires only a defined fertilization media, transfection quality DNA, and incubation with spermatozoa.

Animals↗
PubMed2000

Tamoxifen-bound estrogen receptor (ER) strongly interacts with the nuclear matrix protein HET/SAF-B, a novel inhibitor of ER-mediated transactivation.

The estrogen receptor (ER) is a ligand-dependent transcription factor that acts in a cell- and promoter-specific manner. Evidence suggests that the activity of the ER can be regulated by a number of other stimuli (e.g. growth factors) and that the effects of the ER are modulated by nuclear factors termed coregulators. While the interplay among these factors may in part explain the pleiotropic effects elicited by the ER, there are several other less well described mechanisms of control, such as interactions with the nuclear matrix. Here we report that the nuclear matrix protein/scaffold attachment factor HET/SAF-B is an ER-interacting protein. ER and HET/SAF-B interact in in vitro binding assays, with HET binding to both the ER DNA-binding domain and the hinge region. Coimmunoprecipitation experiments reveal that HET/SAF-B and ER associate in cell lines in the presence or absence of estradiol, but binding is increased by the antiestrogen tamoxifen. HET/SAF-B enhances tamoxifen antagonism of estrogen-induced ER-mediated transactivation, but at high concentrations can inhibit both estrogen and tamoxifen-induced ER activity. HET/SAF-B-mediated repression of ER activity is dependent upon interaction with the ER-DBD. While the existence of high-affinity binding sites for the ER in the nuclear matrix has been known for some time, we now provide evidence of a specific nuclear matrix protein binding to the ER. Furthermore, our data showing that HET/SAF-B binds to ER particularly strongly in the presence of tamoxifen suggests that it may be important for the antagonist effect of tamoxifen.

Adenocarcinoma↗
PubMed2002

Nuclear matrix proteins as biomarkers in prostate cancer.

The nuclear matrix (NM) is the structural framework of the nucleus that consists of the peripheral lamins and pore complexes, an internal ribonucleic protein network, and residual nucleoli. The NM contains proteins that contribute to the preservation of nuclear shape and its organization. These protein components better known as the NM proteins have been demonstrated to be tissue specific, and are altered in many cancers, including prostate cancer. Alterations in nuclear morphology are hallmarks of cancer and are believed to be associated with changes in NM protein composition. Prostate cancer is the most frequently diagnosed cancer in American men and many investigators have identified unique NM proteins that appear to be specific for this disease. These NM protein changes are associated with the development of prostate cancer, as well as in some cases being indicative of cancer stage. Identification of these NM proteins specific for prostate cancer provides an insight to understanding the molecular changes associated with this disease. This article reviews the role of NM proteins as tumor biomarkers in prostate cancer and the potential application of these proteins as therapeutic targets in the treatment of this disease.

Adenocarcinoma↗
PubMed2000

Nuclear matrix proteins as cancer markers.

The transformation of normal cells to a malignant state has long been detected by light microscopy as visible changes in nuclear morphology. These changes include abnormal nuclear shape, increased nuclear to cytoplasmic ratio, and the presence of additional and abnormal nucleoli. Metaplasia,dysplasia, carcinoma-in-situ, and gross malignant tumors are diagnosed and graded pathologically by this traditional method. The resulting relative increase in DNA concentration within these cells produces a greater affinity for Hematoxilyn and Eosin staining, and thus, the characteristic blue color of cancerous tissues. As understanding of the cell structure expanded, the nuclear matrix emerged as an integral component of genetic processing and therefore, became an important cellular entity for study of malignant transformation. Also, several types of cancer have revealed discreet alterations in their respective nuclear matrices. One potential application of these nuclear matrix changes is development of detection and monitoring tests that would reveal the presence of abnormal cells. These tests could be utilized at a number of points in the disease process including prior to gross physical symptoms, and thereby significantly reduce patient morbidity and mortality. A second potential application of the nuclear matrix is to utilize it as a tissue specific protein targeting system to address narrowly directed therapeutic treatments, and thereby avoid the systemic side effects from broad-spectrum therapies like radiation. This paper addresses the role of the nuclear matrix in both normal cells and transformed cells, and highlights several research efforts that have advanced the ability to detect, track, and potentially treat neoplasms at the molecular level. J. Cell. Biochem. Suppl. 35:136-141, 2000.

Animals↗
PubMed1999

Morphological and biochemical analysis of anti-nuclear matrix protein antibodies in human sera.

Autoimmune sera have been used in the diagnosis of autoimmune diseases as well as the analysis of nuclear substructures. In an attempt to study the biological characteristics of the nuclear matrix, we screened human sera using immunofluorescent staining and immunoblot. We detected antibodies against nuclear matrix (NM), a remnant nonchromatin protein compartment after the treatment of detergent, salt and nuclease, in 212 out of 284 tested sera (74.6%) by immunoblot. Peptides with molecular weights of 70 kDa, 50 kDa and 25 kDa were detected in the order of frequency. Clinical informations of 198 out of 212 cases were available and went as follows: 38 cases were autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis; 132 non-autoimmune and non-neoplastic diseases; 16 neoplastic diseases and 12 cases unclassified. The immunofluorescent staining intensity by anti-nuclear matrix protein (NMP) antibodies decreased variably, but fibrillogranular, speckled and nucleolar immunolocalization patterns were retained after in situ fractionation. Ku70 and La protein were detected by anti-NMP antibodies. Immunolocalization by anti-NMP antibodies indicates that the NMPs constitute a variety of characteristic nuclear substructures and may serve as autoantigens in diverse human diseases. In addition, the presence of Ku70 and La protein as NMPs suggests that the NM can be functionally active in association with DNA or RNA.

Antigens, Nuclear↗
PubMed1998

Differentiation-specific nuclear matrix proteins cross-linked to DNA by cis-diammine dichloroplatinum.

DNA-protein cross-linkages were performed in intact undifferentiated and differentiated-HL60 cells by the action of cis-diammine dichloroplatinum. Total nuclear matrix proteins and DNA cross-linked nuclear matrix proteins were resolved by two-dimensional gel electrophoresis. The comparison of the electrophoretic patterns allowed the identification of a set of differentiation-induced nuclear matrix proteins cross-linked to DNA. One of these proteins binds cloned histone SAR sequences. Our results outline an experimental strategy for isolating and characterizing nuclear matrix components that may play a fundamental role in the overall control and coordination of gene expression during differentiation.

Antigens, Nuclear↗
PubMed2003

Cell cycle dependent regulation of protein kinase CK2 signaling to the nuclear matrix.

Protein kinase CK2 is a ubiquitous protein serine/threonine kinase that is involved in cell growth and proliferation as well as suppression of apoptosis. Several studies have suggested that the kinase plays a role in cell cycle progression; however, changes in enzyme activity during phases of cell cycle have not been detected. Nuclear matrix is a key locus for CK2 signaling in the nucleus. We therefore examined CK2 signaling to the nuclear matrix in distinct phases of cell cycle by employing synchronized ALVA-41 prostate cancer cells. Removal of serum from the culture medium resulted in G0/G1 arrest, and a reduction in the nuclear matrix-associated CK2 activity which was rapidly reversed on addition of serum. Arresting the cells in G(0)/G(1) phase with hydroxyurea and subsequent release to S phase by serum gave similar results. Cells arrested in the G(2)/M phase by treatment with nocodazole demonstrated an extensive reduction in the nuclear matrix-associated CK2 which was reversed rapidly on addition of serum. Changes in the immunoreactive CK2 protein were concordant with the activity data reflecting a dynamic trafficking of the kinase in distinct phases of cell cycle. Under the same conditions, CK2 activity in total cellular lysate remained essentially unaltered. These results provide the first direct evidence of discrete modulations of CK2 in the nuclear matrix during the cell cycle progression. Inducible overexpression of CK2 in CHO cells yielded only a modest increase in CK2 activity even though a significant increase in expression was apparent at the level of CK2 alpha-specific message. Stably transfected ALVA-41 cells, however, did not show a significant change in CK2 levels despite increased expression at the message level. Not surprisingly, both types of the stably transfected cells failed to show any alteration in cell cycle progression. Distribution of the CK2 activity in the cytosolic versus nuclear matrix fractions in normal cells appears to be different from that in the cancer cells such that the ratio of nuclear matrix to cytosolic activity is much higher in the latter. Considering that nuclear matrix is central to several nuclear functions, this pattern of intracellular distribution of CK2 may have implications for its role in the oncogenic process. Published 2003 Wiley-Liss, Inc.

Animals↗
PubMedDate not supplied

[Binding of glucocorticoids and glucocorticoid-receptor complexes with rat liver nuclear matrix].

Studies on binding glucocorticoids and cytosol glucocorticoid-receptor complexes with rat liver nuclear matrix were conducted. Zones of binding 3H-dexamethasone and 3H-dexamethasone-receptor complexes, characterized by saturability and high affinity, were found in nuclear matrix structures. A lower level of binding was noted during incubation of nuclear matrix and cytosol from the liver of rats aged 24 mos. than in the use of the same subcellular fractions isolated from the liver of rats aged 6 mos.

Aging↗
PubMed1993

Inhibition of prostate cancer growth by estramustine and etoposide: evidence for interaction at the nuclear matrix.

Metastatic prostate cancer which is refractory to hormone therapy remains an incurable disease for which there is no effective therapy. We have begun to investigate the nuclear matrix, the RNA-protein network of the nucleus that plays an important role in DNA replication and gene expression, as a target for cancer chemotherapy. It was postulated that estramustine phosphate (EMP), an estradiol-nitrogen mustard conjugate that binds to the nuclear matrix, might enhance the cytotoxicity of etoposide (VP-16), a topoisomerase II inhibitor that acts at the level of the nuclear matrix. In a nascent DNA synthesis assay, EMP and etoposide interact to selectively inhibit new DNA synthesis on the nuclear matrix. In vitro, EMP and etoposide appeared to act synergistically to inhibit the growth of the metastatic Dunning rat prostate adenocarcinoma cell line Mat-LyLu as well as the metastatic human prostate adenocarcinoma cell line PC-3. In vivo, EMP and etoposide inhibited prostate adenocarcinoma growth in the Dunning Copenhagen rat model. These data have formed the basis of a Phase I/II clinical trial to examine the effect of EMP and etoposide in patients with stage D hormone-refractory prostate cancer.

Adenocarcinoma↗
PubMed1999

Effect of retinoic acid on the changes of nuclear matrix in termediate filament system in gastric carcinoma cells.

AIM:To explore the relationship between the configuration changes of the nuclear matrix intermediate filament system in cancer cell induced by retinoic acid and the malignant phenotypic reversion of cancer cells.METHODS:The human gastric adenocarcinoma cell line MGc80-3 cells were induced with 10(-6) mol/L retinoic acid and subcultured at cover slip strip and gold grids. The cells were treated by selective extraction method and prepared for whole mount electron microscopy observation. The samples were examined respectively with scanning and transmission electron microscope.RESULTS:The nuclear matrix filaments and intermediate filaments in MGc80-3 cells were relatively few and scattered, not well-distributed and arranged irregularly. The nuclear lamina was ununiformly thick and compact, connected to the nuclear matrix filaments and intermediate filaments relaxedly. However, the two kinds of filaments were abundant and well-distributed, different in slender and thick form and interweaved into a regular network in the cells induced by 10(-6)mol/L RA. The nuclear matrix filaments and inter-mediate filaments were connected closely by the thin and compact fiber-like lamina, and interlaced into a regular network throughout the whole cell region.CONCLUSION:The NM-IF system in MGc80-3 cells had undergone a restorational change similar to those of normal cells after RA inducement. This alternation is an important mor-phological and functional expression to the malignant phenotypic reversion of cancer cells.

Journal Article↗
PubMed1991

Nuclear matrins: identification of the major nuclear matrix proteins.

A preparative two-dimensional polyacrylamide gel system was used to separate and purify the major Coomassie blue-stained proteins from the isolated rat liver nuclear matrix. Approximately 12 major proteins were consistently found. Of these, 5 proteins represented identified proteins, including nuclear lamins A, B, and C, the nucleolar protein B-23, and residual components of core heterogeneous nuclear ribonucleoproteins. The remaining eight major proteins termed the nuclear matrins consisted of matrin 3 (125 kDa, slightly acidic), matrin 4 (105 kDa, basic), matrins D-G (60-75 kDa, basic), and matrins 12 and 13 (42-48 kDa, acidic). Peptide mapping and two-dimensional immunoblot studies indicate that matrins D-G compose two pairs of related proteins (matrins D/E and F/G) and that none of the matrins resemble the nuclear lamins or any of the other major proteins detected on our two-dimensional gels. Subfractionation immunoblot experiments demonstrated the nearly exclusive localization of matrins F/G and other matrins to the nuclear matrix fraction of the cell. These results were further supported by indirect immunofluorescence microscopy that showed a strictly interior nuclear localization of the matrins in intact cells in contrast to the peripherally located nuclear lamins. We conclude that the nuclear matrins are a major class of proteins of the nuclear matrix interior and are distinct from the nuclear lamins.

Animals↗