tailieunhanh - Báo cáo khoa học: Characterization of the angiogenic activity of zebrafish ribonucleases

Ribonucleases identified from zebrafish possess angiogenic and bactericidal activities. Zebrafish RNases have three intramolecular disulfide bonds, a characteristic structural feature of angiogenin, different from the typical four disulfide bonds of the other members of the RNase A superfamily. They also have a higher degree of sequence homology to angiogenin than to RNase A. | Characterization of the angiogenic activity of zebrafish ribonucleases Daria M. Monti1 Wenhao Yu2 Elio Pizzo1 Kaori Shima2 Miaofen G. Hu3 Chiara Di Malta1 Renata Piccoli1 Giuseppe D Alessio1 and Guo-Fu Hu2 1 Department of Structuraland FunctionalBiology University of Naples Federico II Italy 2 Department of Pathology Harvard Medical School Boston MA USA 3 Molecular Oncology Research Institute Tufts MedicalCenter Boston MA USA Keywords amyotrophic lateral sclerosis angiogenesis angiogenin ribonuclease zebrafish Correspondence . Hu Department of Pathology Harvard Medical School 77 Avenue Louis Pasteur Boston MA 02115 USA Fax 1 617 432 6580 Tel 1 617 432 6582 E-mail guofu_hu@ Received 19 March 2009 revised 4 May 2009 accepted 27 May 2009 doi Ribonucleases identified from zebrafish possess angiogenic and bactericidal activities. Zebrafish RNases have three intramolecular disulfide bonds a characteristic structural feature of angiogenin different from the typical four disulfide bonds of the other members of the RNase A superfamily. They also have a higher degree of sequence homology to angiogenin than to RNase A. It has been proposed that all RNases evolved from these angiogenin-like progenitors. In the present study we characterize in detail the function of zebrafish RNases in various steps in the process of angiogenesis. We report that zebrafish RNase-1 -2 and -3 bind to the cell surface specifically and are able to compete with human angiogenin. Similar to human angiogenin all three zebrafish RNases are able to induce phosphorylation of extracellular signal-regulated kinase 1 2 mitogen-activated protein kinase. They also undergo nuclear translocation accumulate in the nucleolus and stimulate rRNA transcription. However zebrafish RNase-3 is defective in cleaving rRNA precursor even though it has been reported to have an open active site and has higher enzymatic activity toward more classic RNase substrates such as .