Nuclear translocation of angiogenin in proliferating
endothelial cells is essential to its angiogenic activity. |
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| Authors: | J Moroianu and J F Riordan |
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| Affiliation: | Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115. |
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| Abstract: | The intracellular pathway of human angiogenin incalf pulmonary artery endothelial (CPAE) cells has been studied byimmunofluorescence microscopy. Proliferating CPAE cells specifically endocytosenative angiogenin and translocate it to the nucleus, where it accumulates in thenucleoli. Nuclear translocation of angiogenin does not occur innonproliferative, confluent CPAE cells. These cells were previously found toexpress an angiogenin-binding protein (AngBP) that was identified as smoothmuscle alpha-actin. Exogenous actin, an anti-actin antibody, heparin, andheparinase treatment all inhibit the internalization of angiogenin, suggestingthe involvement of cell surface AngBP/actin and heparan sulfate proteoglycans inthis process. It has been established that two regions of angiogenin areessential for its angiogenic activity, one is its endothelial cell binding siteand the other its catalytic site capable of cleaving RNA. CPAE cells do notinternalize four enzymatically active angiogenin derivatives whose cell bindingsite is modified, but they do internalize two enzymatically inactive mutantswhose cell binding site is intact. Thus, the putative cell binding site ofangiogenin is necessary for both endocytosis and nuclear translocation, but thecatalytic site is not. Three other angiogenic molecules are also translocated tothe nucleus of growing CPAE cells. Overall, the results suggest that nucleartranslocation of angiogenin and other angiogenic molecules is a critical step inthe process of angiogenesis. |
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