Endothelial-monocyte activating polypeptide II (EMAP II) was initially identified in the supernatant of murine methylcholanthrene A-induced fibrosarcomas (Meth A) by its capacity to activate host effector cells (Kao, J., Ryan, J., Brett, J., Chen, J., Shen, H., Fan, Y-G., Godman, G., Familletti, P., Wang, F., Pan, Y-C., Stern, D., and Clauss, M. (1992) J. Biol. Chem. 267, 20239-20247). Based on the NH2-terminal protein sequence, a full-length cDNA has been cloned which indicates that the precursor of EMAP II is a unique, leaderless, single polypeptide chain with predicted molecular mass ≈34 kDa and that the mature form released by Meth A cells corresponds to ≈20 kDa. Purified recombinant mature EMAP II (EMAP II, ≈20 kDa form) activated endothelial cells with resulting elevation of cytosolic free calcium concentration, release of von Willebrand factor, induction of tissue factor, and expression of the adhesion molecules E-selectin and P-selectin. Neutrophils exposed to EMAP II demonstrated elevated cytosolic free calcium concentration, peroxidase generation, and chemotaxis. EMAP II also activated mononuclear phagocytes elevating cytosolic free calcium concentration, inducing tumor necrosis factor-α (TNF) and tissue factor, and stimulating chemotaxis. Systemic infusion of EMAP II into C3H/HeJ or Balb/c mice was associated with systemic toxicity, pulmonary congestion, and the appearance of TNF, interleukin-1 and -6 in the plasma. A single intra-tumor injection of EMAP II into Meth A sarcomas induced acute thrombohemorrhage and partial tumor regression. Local injection of EMAP II into a tumor resistant to the effects of TNF, murine mammary carcinoma, rendered it sensitive to subsequently administered TNF, which resulted in acute thrombohemorrhage and partial regression. These data suggest that recombinant EMAP II, a tumor-derived cytokine, has properties of a proinflammatory mediator with the capacity to prime the tumor vasculature for a locally destructive process.
"Endothelial Monocyte Activating Polypeptide II (EMAP II, also known as AIMP-1, Scye-1, and p43), a single chain polypeptide protein originally isolated from a murine fibrosarcoma, is ubiquitously expressed as a 34-kDa intracellular protein . On the cell surface, it undergoes proteolytic cleavage ,  to generate a ≈22-kDa C-terminal peptide , ,  that functions as a potent anti-angiogenic protein , . As an extracellular molecule, C-terminal EMAP II (ct-EMAP II) is known to activate endothelial cells, neutrophils and mononuclear phagocytes , ; consequently, ct-EMAP II has shown the capacity to prime tumor vasculature for a locally destructive process, or to be anti-angiogenic in its own capacity , , , . "
[Show abstract][Hide abstract] ABSTRACT: Endothelial-Monocyte Activating Polypeptide (EMAP II) is a secreted protein with well-established anti-angiogenic activities. Intracellular EMAP II expression is increased during fetal development at epithelial/mesenchymal boundaries and in pathophysiologic fibroproliferative cells of bronchopulmonary dysplasia, emphysema, and scar fibroblast tissue following myocardial ischemia. Precise function and regulation of intracellular EMAP II, however, has not been explored to date.
Here we show that high intracellular EMAP II suppresses cellular proliferation by slowing progression through the G2M cell cycle transition in epithelium and fibroblast. Furthermore, EMAP II binds to and is phosphorylated by Cdk1, and exhibits nuclear/cytoplasmic partitioning, with only nuclear EMAP II being phosphorylated. We observed that extracellular secreted EMAP II induces endothelial cell apoptosis, where as excess intracellular EMAP II facilitates epithelial and fibroblast cells migration.
Our findings suggest that EMAP II has specific intracellular effects, and that this intracellular function appears to antagonize its extracellular anti-angiogenic effects during fetal development and pulmonary disease progression.
PLoS ONE 03/2012; 7(3):e33101. DOI:10.1371/journal.pone.0033101 · 3.23 Impact Factor
"HisZ HisRS   AlaX AlaRS   PrdX (ProX) ProRS   GluX (YadB) GluRS  CTP Class I ARS  ATPS Class I ARS  EMAP-II MetRS, TyrRS    Arc1p MetRS, TyrRS  Trbp111 MetRS, TyrRS  BirA SerRS   AsnA AspRS, AsnRS   ThrRS-ed ThrRS  Gcn2 HisRS  Pol gamma B GlyRS  PoxA/GenX LysRS  E.M. Novoa et al. / FEBS Letters 584 (2010) 460–466 461 Fig. 2. Phylogenetic distribution and relative abundance of the 11 bacterial ARS-like proteins considered in this work. Each tree is labeled according to the protein whose distribution is being analyzed. "
[Show abstract][Hide abstract] ABSTRACT: During their extended evolution genes coding for aminoacyl-tRNA synthetases (ARS) have experienced numerous instances of duplication, insertion and deletion of domains. The ARS-related proteins that have resulted from these genetic events are generally known as aminoacyl-tRNA synthetase-like proteins (ARS-like). This heterogeneous group of polypeptides carries out an equally varied number of functions that need not be related to gene translation. Several of these proteins remain uncharacterized. At least 16 different ARS-like proteins have been identified to date, but their functions remain incompletely understood. Here we review the individual phylogenetic distribution of these proteins in bacteria, and apply a new genomics method to determine their potential implication in pathogenicity.
"Of particular interest, is the combination of TNF-a with other agents, either as a way to increase the tumour sensitivity to TNF-a or to enhance the activity of traditional chemotherapeutics. Endothelial-monocyte activating polypeptide II (EMAP-II) is a tumour derived cytokine that, in low doses, can sensitize tumours to the effects of TNF-a (Kao et al, 1994; Marvin et al, 1996; Gnant et al, 1999; Wu et al, 1999). The combination of low-dose EMAP-II with tumour vasculature targeted TNF-a inhibited growth of murine lymphoma and murine melanoma tumours (Crippa et al, 2008). "
[Show abstract][Hide abstract] ABSTRACT: Cancer therapy is in the midst of a major paradigm shift. Traditionally, cancer treatments have focused on tumour cells. However, studies over the past few decades have demonstrated that cancer is a vastly complex entity with multiple components affecting a tumour's growth, invasion and metastasis. These components, collectively termed the 'tumour microenvironment', include endothelial cells, pericytes, fibroblasts, inflammatory cells, leucocytes and elements of the extracellular matrix (ECM). Biological agents that target components of the tumour microenvironment may provide an interesting alternative to traditional tumour cell-directed therapy. Because of the complexity of the tumour milieu, the most beneficial therapy will likely involve the combination of one or more agents directed at this new target. This review highlights recent preclinical and clinical studies involving agents that target tumour vasculature, leucocytes, pericytes, cancer-associated fibroblasts and ECM components. We pay particular attention to combination therapies targeting multiple components of the tumour microenvironment, and aim to demonstrate that this strategy holds promise for the future of cancer treatment.
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