scholarly journals The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts

2005 ◽  
Vol 171 (3) ◽  
pp. 559-568 ◽  
Author(s):  
Viktor Todorovicç ◽  
Chih-Chiun Chen ◽  
Nissim Hay ◽  
Lester F. Lau
Keyword(s):  
Cell Adhesion ◽  
Cell Survival ◽  
Matrix Protein ◽  
De Novo ◽  
Cell Types ◽  
Cellular Interaction ◽  
Cytochrome C Release ◽  
The Matrix ◽  
Promote Cell Survival ◽  
Integrin Α6β1

Integrin-mediated cell adhesion to extracellular matrix proteins is known to promote cell survival, whereas detachment from the matrix can cause rapid apoptotic death in some cell types. Contrary to this paradigm, we show that fibroblast adhesion to the angiogenic matrix protein CCN1 (CYR61) induces apoptosis, whereas endothelial cell adhesion to CCN1 promotes cell survival. CCN1 induces fibroblast apoptosis through its adhesion receptors, integrin α6β1 and the heparan sulfate proteoglycan (HSPG) syndecan-4, triggering the transcription-independent p53 activation of Bax to render cytochrome c release and activation of caspase-9 and -3. Neither caspase-8 activity nor de novo transcription or translation is required for this process. These results show that cellular interaction with a specific matrix protein can either induce or suppress apoptosis in a cell type–specific manner and that integrin α6β1-HSPGs can function as receptors to induce p53-dependent apoptosis.

scholarly journals Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts

2004 ◽  
Vol 167 (5) ◽  
pp. 973-983 ◽  
Author(s):  
Satoshi Fukumoto ◽  
Takayoshi Kiba ◽  
Bradford Hall ◽  
Noriyuki Iehara ◽  
Takashi Nakamura ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Matrix Protein ◽  
Oral Epithelium ◽  
Enamel Matrix Protein ◽  
Mineralized Tissues ◽  
The Matrix ◽  
A Cell ◽  
Dental Epithelium

Tooth morphogenesis results from reciprocal interactions between oral epithelium and ectomesenchyme culminating in the formation of mineralized tissues, enamel, and dentin. During this process, epithelial cells differentiate into enamel-secreting ameloblasts. Ameloblastin, an enamel matrix protein, is expressed by differentiating ameloblasts. Here, we report the creation of ameloblastin-null mice, which developed severe enamel hypoplasia. In mutant tooth, the dental epithelium differentiated into enamel-secreting ameloblasts, but the cells were detached from the matrix and subsequently lost cell polarity, resumed proliferation, and formed multicell layers. Expression of Msx2, p27, and p75 were deregulated in mutant ameloblasts, the phenotypes of which were reversed to undifferentiated epithelium. We found that recombinant ameloblastin adhered specifically to ameloblasts and inhibited cell proliferation. The mutant mice developed an odontogenic tumor of dental epithelium origin. Thus, ameloblastin is a cell adhesion molecule essential for amelogenesis, and it plays a role in maintaining the differentiation state of secretory stage ameloblasts by binding to ameloblasts and inhibiting proliferation.

scholarly journals Characterization of human osteoblast and megakaryocyte-derived osteonectin (SPARC)

Blood ◽  
1992 ◽  
Vol 80 (12) ◽  
pp. 3112-3119
Author(s):  
RJ Jr Kelm ◽  
GA Hair ◽  
KG Mann ◽  
BW Grant
Keyword(s):  
De Novo ◽  
Blood Platelets ◽  
Bone Matrix ◽  
Cell Types ◽  
Sensitivity Analyses ◽  
Complex Type ◽  
Oligosaccharide Structure ◽  
The Matrix

Osteonectin is an adhesive, cell, and extracellular matrix-binding glycoprotein found primarily in the matrix of bone and in blood platelets in vivo. Osteonectins isolated from these two sources differ with respect to the complexity of their constituent N-linked oligosaccharide. In this study, osteonectin synthesized by bone-forming cells (osteoblasts) and platelet-producing cells (megakaryocytes) in vitro was analyzed to determine if the proteins produced were analogous in terms of glycosylation to those isolated from bone and platelets, respectively. Immunoblot analyses of osteonectin produced by the osteoblast-like cell lines, SaOS-2 and MG-63, indicated that secreted and intracellular forms of the molecule are structurally distinct. Endoglycosidase treatment and immunoblotting of osteonectin secreted from SaOS-2 and MG-63 cells, under serum-deprived conditions, suggested that the molecule possessed a complex type oligosaccharide unlike the high-mannose moiety found on bone matrix-derived osteonectin. Biosynthetic labeling of SaOS-2 cells and human megakaryocytes indicated that both cell types synthesize osteonectin de novo. Electrophoretic and glycosidase sensitivity analyses of [35S]-osteonectin isolated from lysates of metabolically labeled SaOS-2 cells and megakaryocytes indicated that these two cell types synthesize osteonectin molecules that are identical in oligosaccharide structure to the isolated bone and platelet proteins. These data suggest that the intracellular form of the osteonectin molecule is glycosylated differently in SaOS-2 cells and megakaryocytes but that the extracellular form which is secreted from platelets in vivo and osteoblasts in vitro is characterized by the presence of a complex type N-linked oligosaccharide.

scholarly journals Acetylation Suppresses the Proapoptotic Activity of GD3 Ganglioside

2002 ◽  
Vol 196 (12) ◽  
pp. 1535-1541 ◽  
Author(s):  
Florence Malisan ◽  
Luigi Franchi ◽  
Barbara Tomassini ◽  
Natascia Ventura ◽  
Ivano Condò ◽  
...  
Keyword(s):  
Sialic Acid ◽  
De Novo ◽  
Cell Types ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Acetyl Esterase ◽  
Gd3 Synthase ◽  
Cellular Apoptosis ◽  
Gd3 Ganglioside ◽  
Different Cell Types

GD3 synthase is rapidly activated in different cell types after specific apoptotic stimuli. De novo synthesized GD3 accumulates and contributes to the apoptotic program by relocating to mitochondrial membranes and inducing the release of apoptogenic factors. We found that sialic acid acetylation suppresses the proapoptotic activity of GD3. In fact, unlike GD3, 9-O-acetyl-GD3 is completely ineffective in inducing cytochrome c release and caspase-9 activation on isolated mitochondria and fails to induce the collapse of mitochondrial transmembrane potential and cellular apoptosis. Moreover, cells which are resistant to the overexpression of the GD3 synthase, actively convert de novo synthesized GD3 to 9-O-acetyl-GD3. The coexpression of GD3 synthase with a viral 9-O-acetyl esterase, which prevents 9-O-acetyl-GD3 accumulation, reconstitutes GD3 responsiveness and apoptosis. Finally, the expression of the 9-O-acetyl esterase is sufficient to induce apoptosis of glioblastomas which express high levels of 9-O-acetyl-GD3. Thus, sialic acid acetylation critically controls the proapoptotic activity of GD3.

scholarly journals Characterization of human osteoblast and megakaryocyte-derived osteonectin (SPARC)

Blood ◽  
1992 ◽  
Vol 80 (12) ◽  
pp. 3112-3119 ◽  
Author(s):  
RJ Jr Kelm ◽  
GA Hair ◽  
KG Mann ◽  
BW Grant
Keyword(s):  
De Novo ◽  
Blood Platelets ◽  
Bone Matrix ◽  
Cell Types ◽  
Sensitivity Analyses ◽  
Complex Type ◽  
Oligosaccharide Structure ◽  
The Matrix

Abstract Osteonectin is an adhesive, cell, and extracellular matrix-binding glycoprotein found primarily in the matrix of bone and in blood platelets in vivo. Osteonectins isolated from these two sources differ with respect to the complexity of their constituent N-linked oligosaccharide. In this study, osteonectin synthesized by bone-forming cells (osteoblasts) and platelet-producing cells (megakaryocytes) in vitro was analyzed to determine if the proteins produced were analogous in terms of glycosylation to those isolated from bone and platelets, respectively. Immunoblot analyses of osteonectin produced by the osteoblast-like cell lines, SaOS-2 and MG-63, indicated that secreted and intracellular forms of the molecule are structurally distinct. Endoglycosidase treatment and immunoblotting of osteonectin secreted from SaOS-2 and MG-63 cells, under serum-deprived conditions, suggested that the molecule possessed a complex type oligosaccharide unlike the high-mannose moiety found on bone matrix-derived osteonectin. Biosynthetic labeling of SaOS-2 cells and human megakaryocytes indicated that both cell types synthesize osteonectin de novo. Electrophoretic and glycosidase sensitivity analyses of [35S]-osteonectin isolated from lysates of metabolically labeled SaOS-2 cells and megakaryocytes indicated that these two cell types synthesize osteonectin molecules that are identical in oligosaccharide structure to the isolated bone and platelet proteins. These data suggest that the intracellular form of the osteonectin molecule is glycosylated differently in SaOS-2 cells and megakaryocytes but that the extracellular form which is secreted from platelets in vivo and osteoblasts in vitro is characterized by the presence of a complex type N-linked oligosaccharide.

scholarly journals Evolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin

2020 ◽  
Vol 118 (2) ◽  
pp. e2021366118
Author(s):  
Francesca Caccuri ◽  
Pasqualina D’Ursi ◽  
Matteo Uggeri ◽  
Antonella Bugatti ◽  
Pietro Mazzuca ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Molecular Mimicry ◽  
Cell Types ◽  
Biological Data ◽  
Matrix Proteins ◽  
Target Cells ◽  
Human Erythropoietin ◽  
The Matrix ◽  
The Difference ◽  
Hiv 1

The HIV-1 matrix protein p17 (p17) is a pleiotropic molecule impacting on different cell types. Its interaction with many cellular proteins underlines the importance of the viral protein as a major determinant of human specific adaptation. We previously showed the proangiogenic capability of p17. Here, by integrating functional analysis and receptor binding, we identify a functional epitope that displays molecular mimicry with human erythropoietin (EPO) and promotes angiogenesis through common beta chain receptor (βCR) activation. The functional EPO-like epitope was found to be present in the matrix protein of HIV-1 ancestors SIV originated in chimpanzees (SIVcpz) and gorillas (SIVgor) but not in that of HIV-2 and its ancestor SIVsmm from sooty mangabeys. According to biological data, evolution of the EPO-like epitope showed a clear differentiation between HIV-1/SIVcpz-gor and HIV-2/SIVsmm branches, thus highlighting this epitope on p17 as a divergent signature discriminating HIV-1 and HIV-2 ancestors. P17 is known to enhance HIV-1 replication. Similarly to other βCR ligands, p17 is capable of attracting and activating HIV-1 target cells and promoting a proinflammatory microenvironment. Thus, it is tempting to speculate that acquisition of an epitope on the matrix proteins of HIV-1 ancestors capable of triggering βCR may have represented a critical step to enhance viral aggressiveness and early human-to-human SIVcpz/gor dissemination. The hypothesis that the p17/βCR interaction and βCR abnormal stimulation may also play a role in sustaining chronic activation and inflammation, thus marking the difference between HIV-1 and HIV-2 in term of pathogenicity, needs further investigation.

scholarly journals HIFα independent mechanisms in renal carcinoma cells modulate divergent outcomes in fibronectin assembly mediated by hypoxia and CoCl2

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Carina Magdaleno ◽  
Leah Dixon ◽  
Narendiran Rajasekaran ◽  
Archana Varadaraj
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Matrix Protein ◽  
Tumor Hypoxia ◽  
Cell Types ◽  
Low Oxygen ◽  
Core Matrix ◽  
New Findings ◽  
The Matrix

Abstract Fibronectin (FN) is a core matrix protein that assembles to form a dynamic cellular scaffold, frequently perturbed during oncogenic transformation. Tumor hypoxia, characterized by low oxygen concentrations in the microenvironment of most solid tumors has been shown to accelerate FN assembly in fibroblasts and cancer-associated fibroblasts, cell types that produce abundant amounts of FN protein. Nevertheless, FN matrix regulation in epithelial cancer cells during hypoxia remains less well defined. In this study we investigate the assembly of the FN matrix during hypoxia in renal cancer epithelial cells, the cells of origin of renal cell carcinoma (RCC). We show that hypoxia (1% O2) specifically increases matrix disassembly and increases migratory propensity in renal cancer cells. However, HIFα stabilization using hypoxia mimetics, does not recapitulate the effect of hypoxia on FN matrix reorganization or cell migration. Using a combination of knockdown and inhibitor-based approaches, our work characterizes the signaling events that mediate these two disparate changes on the matrix and explores its functional significance on chemotactic cell migration. Our study systematically reexamines the role of hypoxia mimetics as experimental substitutes for hypoxia and provides new findings on HIFα stabilization and the FN matrix in the context of renal cancer.

scholarly journals MT1-MMP-dependent cell migration: proteolytic and non-proteolytic mechanisms

2019 ◽  
Vol 47 (3) ◽  
pp. 811-826 ◽  
Author(s):  
Valentina Gifford ◽  
Yoshifumi Itoh
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Matrix Metalloproteinase ◽  
Cell Motility ◽  
Cell Types ◽  
Migration And Invasion ◽  
Type I ◽  
The Matrix ◽  
Increase Cell Motility ◽  
Dependent Cell

Abstract Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a type I transmembrane proteinase that belongs to the matrix metalloproteinase (MMP) family. It is a potent modifier of cellular microenvironment and promotes cell migration and invasion of a wide variety of cell types both in physiological and pathological conditions. It promotes cell migration by degrading extracellular matrix on the cell surface and creates a migration path, by modifying cell adhesion property by shedding cell adhesion molecules to increase cell motility, and by altering cellular metabolism. Thus, MT1-MMP is a multifunctional cell motility enhancer. In this review, we will discuss the current understanding of the proteolytic and non-proteolytic mechanism of MT1-MMP-dependent cell migration.

Observations with the electron microscope on enameloid formation in the common eel ( Anguilla anguilla ; Teleostei)

1976 ◽  
Vol 194 (1115) ◽  
pp. 253-269 ◽  
Keyword(s):  
Matrix Protein ◽  
Basal Layer ◽  
Tooth Germ ◽  
Anguilla Anguilla ◽  
Cell Types ◽  
Secretory Cells ◽  
Oral Epithelium ◽  
Collagen Fibres ◽  
The Matrix ◽  
Cell Layers

In the eel, the very young tooth germ consisted of an invagination into the oral epithelium, filled with a papilla of mesenchymal cells. The basal layer of the epithelium surrounding the papilla became the inner dental epithelium (i. d. e.). Initially both the i. d. e. and the papilla cells were undifferentiated. Subsequently, the i. d. e. cells and the superficial cells of the papilla differentiated, the latter becoming odontoblasts, and the matrix of cap enameloid was laid down between the two cell layers. Differentiation of the i. d. e. cells and odontoblasts proceeded in parallel, both cell types acquiring the features of secretory cells, namely enlarged nucleoli, abundant rough endoplasmic reticulum, an active Golgi apparatus and numerous vesicles. Confluence of vesicles with the distal cell membranes was observed. These findings indicate that both the i. d. e. and odontoblasts synthesize protein and secrete it into the matrix of cap enameloid, in confirmation of previous studies with autoradiography (Shellis & Miles 1974). The matrix of cap enameloid reached its mature size and shape without becoming mineralized. It contained collagen fibres, odontoblast processes and vesicles. Mineralization of cap enameloid appeared to proceed centrifugally. The crystals were large and ribbon-like, as in enamel, and their orientation conformed with the pattern of collagen fibres of the matrix. The matrix protein, including the fibres, was, however, removed during mineralization, apparently by way of the i. d. e., which showed special features at this stage associated with transport of both protein and mineral. The collar enameloid in this fish was only about 2 μm thick and consisted of two hypermineralized layers. The inner layer appeared to be homologous with the cap enameloid, being formed by the joint activity of odontoblasts and the i. d. e. of Hertwig’s sheath. The outer, more heavily mineralized layer appeared to be produced entirely by the i. d. e. and a similar layer was laid down on the outer surface of the cap enameloid. The teeth of the eel thus bear a layer of enameloid, covered in turn by a much thinner layer which may be homologous with enamel.

scholarly journals Analysis of the Viral Elements Required in the Nuclear Import of HIV-1 DNA

2009 ◽  
Vol 84 (2) ◽  
pp. 729-739 ◽  
Author(s):  
Lise Rivière ◽  
Jean-Luc Darlix ◽  
Andrea Cimarelli
Keyword(s):  
Nuclear Import ◽  
Matrix Protein ◽  
Active Phase ◽  
Cell Types ◽  
Target Cells ◽  
Nuclear Pore ◽  
Viral Dna ◽  
The Matrix ◽  
Central Polypurine Tract ◽  
Hiv 1

ABSTRACT HIV-1 possesses an exquisite ability to infect cells independently from their cycling status by undergoing an active phase of nuclear import through the nuclear pore. This property has been ascribed to the presence of karyophilic elements present in viral nucleoprotein complexes, such as the matrix protein (MA); Vpr; the integrase (IN); and a cis-acting structure present in the newly synthesized DNA, the DNA flap. However, their role in nuclear import remains controversial at best. In the present study, we carried out a comprehensive analysis of the role of these elements in nuclear import in a comparison between several primary cell types, including stimulated lymphocytes, macrophages, and dendritic cells. We show that despite the fact that none of these elements is absolutely required for nuclear import, disruption of the central polypurine tract-central termination sequence (cPPT-CTS) clearly affects the kinetics of viral DNA entry into the nucleus. This effect is independent of the cell cycle status of the target cells and is observed in cycling as well as in nondividing primary cells, suggesting that nuclear import of viral DNA may occur similarly under both conditions. Nonetheless, this study indicates that other components are utilized along with the cPPT-CTS for an efficient entry of viral DNA into the nucleus.

Periodic Structure in the Matrix Protein of an Insect Virus

1982 ◽  
Vol 40 ◽  
pp. 302-303
Author(s):  
H.M. Mazzone ◽  
W.F. Engler ◽  
R. Zerillo ◽  
G.F. Bahr
Keyword(s):  
Inclusion Body ◽  
Periodic Structure ◽  
Matrix Protein ◽  
Malacosoma Disstria ◽  
Insect Virus ◽  
Virus Particles ◽  
The Matrix ◽  
Nucleopolyhedrosis Virus

The nucleopolyhedrosis virus (NPV) of the forest tent cater - pillar (Malacosoma disstria Hubner) has been analyzed in our laboratories. As a representative of the Baculovirus class, the NPV has virus particles enclosed with in a proteinaceous structure, the inclusion body.

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