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Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization

Human RNASET2 (hRNASET2) has been demonstrated to exert antiangiogenic and antitumorigenic effects independent of its ribonuclease capacity. We suggested that RNASET2 exerts its antiangiogenic and antitumorigenic activities via binding to actin and consequently inhibits cell motility. We focused her...

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Autores principales: Nesiel-Nuttman, Liron, Doron, Shani, Schwartz, Betty, Shoseyov, Oded
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341462/
https://www.ncbi.nlm.nih.gov/pubmed/25815360
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author Nesiel-Nuttman, Liron
Doron, Shani
Schwartz, Betty
Shoseyov, Oded
author_facet Nesiel-Nuttman, Liron
Doron, Shani
Schwartz, Betty
Shoseyov, Oded
author_sort Nesiel-Nuttman, Liron
collection PubMed
description Human RNASET2 (hRNASET2) has been demonstrated to exert antiangiogenic and antitumorigenic effects independent of its ribonuclease capacity. We suggested that RNASET2 exerts its antiangiogenic and antitumorigenic activities via binding to actin and consequently inhibits cell motility. We focused herein on the identification of the actin binding site of hRNASET2 using defined sequences encountered within the whole hRNASET2 protein. For that purpose we designed 29 different hRNASET2-derived peptides. The 29 peptides were examined for their ability to bind immobilized actin. Two selected peptides-A103-Q159 consisting of 57 amino acids and peptide K108-K133 consisting of 26 amino acids were demonstrated to have the highest actin binding ability and concomitantly the most potent anti-angiogenic activity. Further analyses on the putative mechanisms associated with angiogenesis inhibition exerted by peptide K108-K133 involved its location during treatment within the HUVE cells. Peptide K108-K133 readily penetrates the cell membrane within 10 min of incubation. In addition, supplementation with angiogenin delays the entrance of peptide K108-K133 to the cell suggesting competition on the same cell internalization route. The peptide was demonstrated to co-localize with angiogenin, suggesting that both molecules bind analogous cellular epitopes, similar to our previously reported data for ACTIBIND and trT2-50.
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spelling pubmed-43414622015-03-26 Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization Nesiel-Nuttman, Liron Doron, Shani Schwartz, Betty Shoseyov, Oded Oncoscience Research Paper Human RNASET2 (hRNASET2) has been demonstrated to exert antiangiogenic and antitumorigenic effects independent of its ribonuclease capacity. We suggested that RNASET2 exerts its antiangiogenic and antitumorigenic activities via binding to actin and consequently inhibits cell motility. We focused herein on the identification of the actin binding site of hRNASET2 using defined sequences encountered within the whole hRNASET2 protein. For that purpose we designed 29 different hRNASET2-derived peptides. The 29 peptides were examined for their ability to bind immobilized actin. Two selected peptides-A103-Q159 consisting of 57 amino acids and peptide K108-K133 consisting of 26 amino acids were demonstrated to have the highest actin binding ability and concomitantly the most potent anti-angiogenic activity. Further analyses on the putative mechanisms associated with angiogenesis inhibition exerted by peptide K108-K133 involved its location during treatment within the HUVE cells. Peptide K108-K133 readily penetrates the cell membrane within 10 min of incubation. In addition, supplementation with angiogenin delays the entrance of peptide K108-K133 to the cell suggesting competition on the same cell internalization route. The peptide was demonstrated to co-localize with angiogenin, suggesting that both molecules bind analogous cellular epitopes, similar to our previously reported data for ACTIBIND and trT2-50. Impact Journals LLC 2014-11-26 /pmc/articles/PMC4341462/ /pubmed/25815360 Text en Copyright: © 2015 Nesiel-Nuttman et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Nesiel-Nuttman, Liron
Doron, Shani
Schwartz, Betty
Shoseyov, Oded
Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization
title Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization
title_full Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization
title_fullStr Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization
title_full_unstemmed Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization
title_short Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization
title_sort human rnaset2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341462/
https://www.ncbi.nlm.nih.gov/pubmed/25815360
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