The human ENO1 gene product (recombinant human α-enolase) displays characteristics required for a plasminogen binding protein

Andronicos, Nicholas M.; Ranson, Marie; Bognacki, John; Baker, Mark S.

doi:10.1016/s0167-4838(96)00146-x

Cited by 53 publications

(55 citation statements)

References 13 publications

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“…α-ENO is a glycolytic enzyme that is a key 2-phospho-D-glycerate hydrolase in the cytoplasm of prokaryotes and eukaryotes. Plasminogen binds α-ENO via its C-terminal lysine residue (20), enhancing its activation and protecting activated plasmin against inhibition by α2-antiplasmin. α-ENO expression enhances plasminogen activation and promotes mammalian cell migration.…”

Section: Resultsmentioning

confidence: 99%

microRNA 17/20 inhibits cellular invasion and tumor metastasis in breast cancer by heterotypic signaling

Willmarth

Zhou

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

222

172

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microRNAs are thought to regulate tumor progression and invasion via direct interaction with target genes within cells. Here the microRNA17/20 cluster is shown to govern cellular migration and invasion of nearby cells via heterotypic secreted signals. micro-RNA17/20 abundance is reduced in highly invasive breast cancer cell lines and node-positive breast cancer specimens. Cell-conditioned medium from microRNA17/20-overexpressing noninvasive breast cancer cell MCF7 was sufficient to inhibit MDA-MB-231 cell migration and invasion through inhibiting secretion of a subset of cytokines, and suppressing plasminogen activation via inhibition of the secreted plasminogen activators (cytokeratin 8 and α-enolase). microRNA17/20 directly repressed IL-8 by targeting its 3′ UTR, and inhibited cytokeratin 8 via the cell cycle control protein cyclin D1. At variance with prior studies, these results demonstrated a unique mechanism of how the altered microRNA17/20 expression regulates cellular secretion and tumor microenvironment to control migration and invasion of neighboring cells in breast cancer. These findings not only reveal an antiinvasive function of miR-17/20 in breast cancer, but also identify a heterotypic secreted signal that mediates the microRNA regulation of tumor metastasis.M icroRNAs (miRNAs) are 21-to 22-nucleotide molecules that regulate cellular phenotype through altering the stability or translational efficiency of targeted mRNAs (1). Important associations between miRNA gene expression and human cancer have implicated miRNA in human tumorigenesis (2-4). miRNA encoding genes are frequently located at fragile sites, common breakpoints, or minimal regions of amplification (5). The human miR-17/20 cluster, located on chromosome 13q31, undergoes loss of heterozygosity in several different cancers, including breast cancer. In the human B cell line P493-6, miR-17/20 inhibits cell growth via suppression of E2F1 expression (6). In mice, transgenic mice overexpressing miR-17 alone showed overall tissue growth retardation, smaller organs, and greatly reduced hematopoietic cell lineages (7). Analysis of miRNAs regulated in cyclin D1 transgenic mammary tumors and reciprocally regulated in cyclin D1-knockout mice identified the miR-17/20 cluster as an important regulatory switch in mammary tumor growth. miR-17/20 inhibited breast cancer tumor growth through repression of cyclin D1 expression via the 3′ UTR binding site (8). Recent evidence implicates miRNA in breast cancer metastasis by inhibiting target genes. miR-335 inhibited human breast cancer cell metastasis via repression of SOX4, a regulator of progenitor cell development and migration (9). miR-10b promotes cell migration in vitro and initiates breast tumor invasion in vivo by targeting gene HOXD10 (10). miR-200 family prevented epithelial to mesenchymal transition of breast cancer cells by repressing ZEB1 and SIP1 (11). However, the role of the miR-17/20 cluster in regulation of breast cancer metastasis remains unknown.Tumor cell migration and invasion is in par...

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Section: Resultsmentioning

confidence: 99%

microRNA 17/20 inhibits cellular invasion and tumor metastasis in breast cancer by heterotypic signaling

Willmarth

Zhou

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

222

172

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“…Porcine Plasminogen Purification-Plasminogen was isolated from porcine plasma as described previously (27,28). MALDI Q-TOF tandem MS, performed according to Henrich et al (26), confirmed the purified protein as plasminogen.…”

Section: Methodsmentioning

confidence: 99%

A Processed Multidomain Mycoplasma hyopneumoniae Adhesin Binds Fibronectin, Plasminogen, and Swine Respiratory Cilia

Seymour¹,

Deutscher

Jenkins

et al. 2010

Journal of Biological Chemistry

134

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Porcine enzootic pneumonia is a chronic respiratory disease that affects swine. The etiological agent of the disease, Mycoplasma hyopneumoniae, is a bacterium that adheres to cilia of the swine respiratory tract, resulting in loss of cilia and epithelial cell damage. A M. hyopneumoniae protein P116, encoded by mhp108, was investigated as a potential adhesin. Examination of P116 expression using proteomic analyses observed P116 as a full-length protein and also as fragments, ranging from 17 to 70 kDa in size. A variety of pathogenic bacterial species have been shown to bind the extracellular matrix component fibronectin as an adherence mechanism. M. hyopneumoniae cells were found to bind fibronectin in a dose-dependent and saturable manner. Surface plasmon resonance was used to show that a recombinant C-terminal domain of P116 bound fibronectin at physiologically relevant concentrations (K D 24 ؎ 6 nM). Plasmin(ogen)-binding proteins are also expressed by many bacterial pathogens, facilitating extracellular matrix degradation. M. hyopneumoniae cells were found to also bind plasminogen in a dose-dependent and saturable manner; the C-terminal domain of P116 binds to plasminogen (K D 44 ؎ 5 nM). Plasminogen binding was abolished when the C-terminal lysine of P116 was deleted, implicating this residue as part of the plasminogen binding site. P116 fragments adhere to the PK15 porcine kidney epithelial-like cell line and swine respiratory cilia. Collectively these data suggest that P116 is an important adhesin and virulence factor of M. hyopneumoniae.

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“…Plasminogen Purification and Labeling-Glu-plasminogen was purified from human plasma using lysine Sepharose-4B affinity chromatography as described previously (12,23). Purified plasminogen was biotinylated by the addition of 10% (v/v) 1 M NaHCO 3 (pH 9), and a 40 M excess of biotin-X-N-hydroxysuccinimide in Me 2 SO (Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

The Maintenance of High Affinity Plasminogen Binding by Group A Streptococcal Plasminogen-binding M-like Protein Is Mediated by Arginine and Histidine Residues within the a1 and a2 Repeat Domains

Sanderson-Smith¹,

Walker

Ranson

2006

Journal of Biological Chemistry

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Subversion of the plasminogen activation system is implicated in the virulence of group A streptococci (GAS). GAS displays receptors for the human zymogen plasminogen on the cell surface, one of which is the plasminogen-binding group A streptococcal M-like protein (PAM). The plasminogen binding domain of PAM is highly variable, and this variation has been linked to host selective immune pressure. Site-directed mutagenesis of full-length PAM protein from an invasive GAS isolate was undertaken to assess the contribution of residues in the a1 and a2 repeat domains to plasminogen binding function. Mutagenesis to alanine of key plasminogen binding lysine residues in the a1 and a2 repeats ( in both the a1 and a2 repeat domains of PAM can mediate high affinity plasminogen binding. These data suggest that highly conserved arginine and histidine residues may compensate for variation elsewhere in the a1 and a2 plasminogen binding repeats, and may explain the maintenance of high affinity plasminogen binding by naturally occurring variants of PAM.The Gram-positive bacterium Streptococcus pyogenes (group A streptococcus, GAS) 3 is responsible for a wide variety of skin and mucosal infections in humans. Current estimates indicate that ϳ1.78 million new cases of severe streptococcal infection occur each year (1). A key feature of invasive GAS infections is

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The human ENO1 gene product (recombinant human α-enolase) displays characteristics required for a plasminogen binding protein

Cited by 53 publications

References 13 publications

microRNA 17/20 inhibits cellular invasion and tumor metastasis in breast cancer by heterotypic signaling

microRNA 17/20 inhibits cellular invasion and tumor metastasis in breast cancer by heterotypic signaling

A Processed Multidomain Mycoplasma hyopneumoniae Adhesin Binds Fibronectin, Plasminogen, and Swine Respiratory Cilia

The Maintenance of High Affinity Plasminogen Binding by Group A Streptococcal Plasminogen-binding M-like Protein Is Mediated by Arginine and Histidine Residues within the a1 and a2 Repeat Domains

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