Abstract: Disclosed herein are methods and compositions for inhibiting neddylation using Glycyl-tRNA synthase (GlyRS) inhibitors. Also disclosed are related compositions and methods for treating diseases such as cancer.

Abstract: Methods, compositions and kits for detecting mutated aminoacyl tRNA synthetase (aaRS) in biological samples from a subject suspect of having or suffering from a Charcot-Marie-Tooth (CMT) disease or a CMT-related disease are disclosed herein. In some embodiments, the methods include determining the amount of mutated aaRS bound to Neuropilin 1 (Nrp1). In some embodiments, methods include detection of endogenous vascular endothelial growth factor (VEGF) bound to Nrp1. Also disclosed are methods, compositions and kits for the diagnosis of a CMT or a CMT-related disease through the detection of VEGF and/or mutated aaRS in a subject.

Abstract: Provided are compositions and methods for the treatment of mutant glycyl-tRNA synthetase (GlyRS)-associated diseases, such as Charcot-Marie-Tooth (CMT) diseases, and related compositions and methods for diagnostic, drug discovery, and research applications. Also provided are mutant glycyl-tRNA synthetases and uses thereof.

Abstract: Methods of enhancing angiogenesis utilizing carboxy-terminal truncated human tyrosyl-tRNA synthetase (TyrRS) are disclosed. The truncated human TyrRS polypeptides comprise residues 1-364 or residues 1-343 of full length human TyrRS (SEQ ID NO: 2).

Abstract: Isolated monomeric aminoacyl-tRNA synthetase polypeptides and polynucleotides having non-canonical biological activities are provided, as well as compositions and methods related thereto.

Abstract: Isolated monomelic aminoacyl-tRNA synthetase polypeptides and polynucleotides having non-canonical biological activities are provided, as well as compositions and methods related thereto.

Abstract: The invention provides an isolated nucleic acid encoding a polypeptide capable of inhibiting angiogenesis or neovascularization, wherein the nucleic acid comprises a first polynucleotide sequence comprising a coding sequence at least 95 percent identical to a sequence selected from the group consisting of a polynucleotide SEQ ID NO:6, a polynucleotide that encodes a polypeptide of SEQ ID NO:12, and a polynucleotide that encodes a fragment of the polypeptide of SEQ ID NO:12; and wherein the nucleic acid does not encode for the amino acid sequence of amino acids 71-93 of SEQ ID NO:1. Pharmaceutical compositions, vectors, and methods for inhibiting neovascularization or angiogenesis comprising or utilizing the nucleic acids also are provided.

Abstract: Methods of enhancing angiogenesis utilizing carboxy-terminal truncated human tyrosyl-tRNA synthetase (TyrRS) are disclosed. The truncated human TyrRS polypeptides comprise residues 1-364 or residues 1-343 of full length human TyrRS (SEQ ID NO: 2).

Abstract: Provided are histidyl-tRNA synthetase variant polypeptides, X-ray crystallographic and NMR spectroscopy structures of HRS polypeptides, and related compositions and methods for therapy and drug discovery.

Abstract: Nucleic acids encoding tRNA synthetase polypeptides useful for regulating angiogenesis are disclosed. Methods of making and using such nucleic acids are also disclosed.

Abstract: Pharmaceutical compositions comprising truncated tryptophanyl-tRNA synthetase polypeptides useful for regulating angiogenesis an nucleic acids encoding such tRNA synthetase polypeptides are described. Methods of making and using such compositions are also disclosed.

Abstract: Isolated monomelic aminoacyl-tRNA synthetase polypeptides and polynucleotides having non-canonical biological activities are provided, as well as compositions and methods related thereto.

Abstract: Pharmaceutical compositions comprising truncated tryptophanyl-tRNA synthetase polypeptides useful for regulating angiogenesis an nucleic acids encoding such tRNA synthetase polypeptides are described. Methods of making and using such compositions are also disclosed.

Abstract: The invention provides an isolated nucleic acid encoding a polypeptide capable of inhibiting angiogenesis or neovascularization, wherein the nucleic acid comprises a first polynucleotide sequence comprising a coding sequence at least 95 percent identical to a sequence selected from the group consisting of a polynucleotide SEQ ID NO:6, a polynucleotide that encodes a polypeptide of SEQ ID NO:12, and a polynucleotide that encodes a fragment of the polypeptide of SEQ ID NO:12; and wherein the nucleic acid does not encode for the amino acid sequence of amino acids 71-93 of SEQ ID NO:1. Pharmaceutical compositions, vectors, and methods for inhibiting neovascularization or angiogenesis comprising or utilizing the nucleic acids also are provided.

Abstract: The present invention provides an isolated polypeptide comprising residues 94-471 of SEQ ID NO: 10, wherein the isolated polypeptide does not comprise amino acid residues 1-47 of SEQ ID NO: 10. Nucleic acids and expression vectors encoding the peptide also are provided.

Abstract: Compositions comprising truncated tryptophanyl-tRNA synthetase polypeptides useful for regulating angiogenesis, as well as nucleic acids encoding such tRNA synthetase polypeptides are described. Methods of making and using such compositions are also disclosed.

Abstract: A method of suppressing angiogenesis in a mammal (e.g., for treating tumors, tumor metastasis or a condition that would benefit from decreased angiogenesis) comprises the step of administering to the mammal an angiostatically effective amount of a pharmaceutical composition comprising an isolated antiangiogenic truncated tryptophanyl-tRNA synthetase (TrpRS) polypeptide or an isolated nucleic acid that comprises a polynucleotide sequence that encodes the truncated TrpRS polypeptide. The truncated TrpRS polypeptide comprises residues 71-471 of SEQ ID NO: 10, residues 48-471 of SEQ ID NO: 10, or a polypeptide of approximately 47 kD molecular weight produced by cleavage of the polypeptide of SEQ ID NO: 10 with polymorphonuclear leucocyte elastase.

Abstract: The invention provides a method for inhibiting ocular neovascularization in a patient. The method comprises administering to a patient an ocular neovascularization inhibiting amount of a water-soluble polypeptide selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 7, and an ocular neovascularization inhibiting fragment thereof, which includes at least one of amino acid residue signature sequences HVGH (SEQ ID NO:10) and KMSAS (SEQ ID NO:11). A method for assaying the angiogenesis inhibiting activity of a composition is also provided.

Abstract: Compositions comprising truncated tryptophanyl-tRNA synthetase polypeptides useful for regulating angiogenesis, as well as nucleic acids encoding such tRNA synthetase polypeptides are described. Methods of making and using such compositions are also disclosed.

Abstract: Compositions comprising truncated tryptophanyl-tRNA synthetase polypeptides useful for regulating angiogenesis, as well as nucleic acids encoding such tRNA synthetase polypeptides are described. Methods of making and using such compositions are also disclosed.