Human angiogenin is rapidly translocated to the nucleus of human umbilical vein endothelial cells and binds to DNA

Abstract

Human angiogenin is translocated to the nucleus of human umbilical vein endothelial cells in a time-dependent manner. Exogenous angiogenin appears in the nucleus in 2 min, reaches saturation in 15 min when 85% of the internalized angiogenin is in the nuclei, and remains associated with the nucleus for at least 4 h. Endothelial cells cultured at low density have a much higher capacity to translocate angiogenin to the nucleus than do those cultured at high density. This observation is consistent with previous findings that both the ability of endothelial cells to proliferate in response to angiogenin and the expression of an angiogenin receptor on the cell surface depend on cell density. Nuclear (125)I-angiogenin is not degraded and is neither spontaneously dissociated nor replaced by unlabeled angiogenin. It is, however, released by deoxyribonuclease I, but not by ribonuclease A, suggesting that angiogenin binds to DNA in the nucleus. These results suggest that in addition to acting as a ribonuclease, angiogenin may play a role in regulating gene expression by direct binding to DNA.

A New Concept for Androgen Receptor-Independent Growth of Prostate Cancer

“…Nuclear translocation of angiogenin in endothelial cells depends strictly on cell density. It decreases as the cell density increases and diminishes when cells are confluent (35). However, nuclear translocation of angiogenin in cancer cells seems to be density-independent (28).…”

An electrochemical functional assay for the sensing of nitric oxide release induced by angiogenic factors

“…* ANG can induce nuclear translocation, i.e. enter the cell nucleus and probably interact with ribonucleotides (49,50).…”

“…However, this compound had no significant inhibitory effect on NO release after ANG stimulation, thus showing that the ribonucleolytic property of ANG is not related to its ability to induce NO release in endothelial cells. Neomycin, an aminoglycoside antibiotic, was used to inhibit ANG nuclear translocation (50,53,54). In particular, this drug has been used to inhibit tumor growth in athymic mice (40).…”

Angiogenin Is Translocated to the Nucleus of HeLa Cells and Is Involved in Ribosomal RNA Transcription and Cell Proliferation

“…Inhibition of nuclear translocation of angiogenin (20) or mutagenesis at its nuclear localization sequence (21) both abolished the angiogenic activity. Nuclear translocation of angiogenin in endothelial cells is rapid (22) and independent of microtubules and lysosomes (23), but is strictly dependent on cell density (22). It decreases as cell density increases and ceases when cells are confluent.…”