mAngiogenin-3, a target gene of oncoprotein E2a-Pbx1, encodes a new angiogenic member of the angiogenin family

Angiogenins are proteins in the pancreatic ribonuclease superfamily that ut ilize their ribonuclease activity to induce formation of new blood vessels. Recently we identified a new member of the angiogenin gene family, mouse a ngiogenin-3, by virtue of its transcriptional activation in NIH3T3 fibrobla sts coincident with transformation by the chimeric leukemia oncogene, E2a-P bx1, Here we have isolated the cDNA encoding mouse angiogenin-3 and used it to produce the protein in E, coli, We demonstrate that mouse angiogenin-3 is a ribonuclease whose activity and specificity towards tRNA and dinucleot ide substrates differ from those of mouse angiogenin or of mouse angiogenin -related protein, a non-angiogenic factor. Mouse angiogenin-3 induced angio genesis in both the chicken embryo chorioallantoic membrane assay and the r at cremaster muscle. Electron microscopy revealed that endothelial cells wi thin vessels induced by both mouse angiogenin-3 and mouse angiogenin contai n fenestrations similar to those observed in endothelial cells from neovasc ulature induced by vascular endothelial growth factor and basic fibroblast growth factor. Mouse angiogenin-3 also induced other molecular events typic al of rapidly proliferating endothelial cells, such as increases in rough e ndoplasmic reticulum, polysomes, and mitochondria.