IndraLab
Statements
sparser
"In the mAb17-treated tumor tissues, nuclear translocation of ANG was inhibited ( xref ), and rRNA transcription was reduced as indicated by a 50% decrease in the number of nucleolar organizer region (NOR) ( xref ), which are loops of rDNA that are actively transcribed to rRNA ( xref )."
sparser
"Classically, after entry into endothelial cells via receptor mediated endocytosis ( xref ), angiogenin translocate into the nucleus and subsequently into the nucleolus where it stimulates rRNA transcription, most important for ribosomal biogenesis and the control of transcription of other angiogenic factors and growth factors ( xref , xref )."
sparser
"This has led a search for less toxic derivatives and analogues of neomycin and led to the finding that neamine, xref a virtually nontoxic derivative of neomycin, has comparable activity in blocking nuclear translocation of ANG. xref Neamine is equally effective in inhibiting angiogenesis and tumor growth induced by ANG as well as by other angiogenic factors. xref , xref Other aminoglycoside antibiotics including streptomycin, gentamicin, kanamycin, amikacin, and paromomycin do not block nuclear translocation of ANG and are not anti-angiogenic. xref "
sparser
"Among these antagonists, agents that target nuclear translocation of angiogenin would be more advantageous and practical than those that target angiogenin directly because angiogenin normally circulates in plasma at a concentration of 250 to 350 ng/ml ( xref , xref ) and would need an exceedingly high dose of direct inhibitor to neutralize it ( xref )."
sparser
"Experimental evidence for this contention includes: i) nuclear translocation of endogenous angiogenin in endothelial cells is stimulated by other angiogenic factors including aFGF, bFGF, VEGF and EGF [ xref ]; ii) knocking down ANG expression in endothelial cells inhibits bFGF- and VEGF-induced cell proliferation, accompanied with a decrease in rRNA transcription."
sparser
"These results, together with the finding that ANG is enhanced in the nucleus of androgen-independent cells, suggest that upregulation and enhanced nuclear translocation of ANG will result in an excessive supply of rRNA, which may contribute to the development of castration resistance."
sparser
"To investigate whether the ALS-associated mutations affect the uptake and translocation of ANG to the nucleus, we exposed the human neuronal cell line SY5Y to hANG and hANG-ALS variants (for which we have determined the 3D structure) and detected uptake by staining with the 26-2F monoclonal antibody to hANG ( xref )."
sparser
"In order to understand the mechanism by which ANG maintains CSC quiescence, we first examined differential subcellular distribution of ANG in CSCs and parent cells of PC3, and found that while ANG was translocated to nucleus and accumulated in the nucleolus in PC3 parent cells, as has been reported previously xref , it was mainly located in stress granules and co-localized with poly(A)-binding protein (PABP), a stress granule marker, in CSCs (Supplementary Fig. xref )."
sparser
"This inhibition was accompanied by a blockade of nuclear translocation of ANG and a decrease in rRNA transcription, consistent with the reports that nuclear function of ANG is related to rRNA transcription and that the neomycin family of aminoglycoside antibiotics blocks nuclear translocation of ANG."
sparser
"Knockdown of PLXNB2 expression in LNCaP cells ( xref ) abolished specific binding of ANG to cell surface ( xref ), inhibited nuclear translocation of ANG ( xref ), and abolished ANG-induced cell proliferation ( xref ), AKT and ERK phosphorylation, and 47S rRNA transcription ( xref )."
sparser
"Indeed, one of the targets of nerve growth factor-triggered PKC phosphorylation is, once again, nucleolin ( xref ), and in a recent investigation evidence was reported that neomycin blocks nuclear translocation of angiogenin by virtue of this antibiotic's inhibitory action on phospholipase C ( xref )."
sparser
"P112L ANG variant, which is found in amyotrophic lateral sclerosis (ALS) patients ( xref ) and which is incapable of nuclear localization, was unable to mediate tiRNA production, indicating that nuclear translocation of ANG, thus the cell surface receptor of ANG, is required for ANG to cleave tRNA in vivo ."
sparser
"Thus, neamine seems to block nuclear translocation of ANG thereby suppressing rRNA transcription, cell proliferation and angiogenesis, consistent with the previous report that ANG plays a dual role in prostate cancer progression by stimulating both angiogenesis and cancer cell proliferation [ xref ]."
reach
"During a study on the mechanism by which angiogenin is translocated to the nucleus of endothelial cells, neomycin, approved by the Food and Drug Administration as an aminoglycoside antibiotic, was found to block nuclear translocation of angiogenin, thereby inhibiting angiogenin induced cell proliferation and angiogenesis."
sparser
"Functionally, we showed that at 30 μg/ml, mAb17 completely blocked nuclear translocation of ANG under growth conditions ( xref ) and SG localization under stress ( xref ), and abolished angiogenic activity of both ANG and VEGF ( xref ) as we have shown before that ANG-mediated rRNA transcription is required for VEGF to induce angiogenesis ( xref )."
sparser
"During a study on the mechanism by which angiogenin is translocated to the nucleus of endothelial cells, neomycin, approved by the Food and Drug Administration as an aminoglycoside antibiotic, was found to block nuclear translocation of angiogenin, thereby inhibiting angiogenin-induced cell proliferation and angiogenesis ( xref )."
sparser
"These results suggest that cross-talk between angiogenin and protein kinase B/Akt signaling pathways is essential for angiogenin-induced angiogenesis in vitro and in vivo, and that angiogenin-induced PKB/Akt activation is independent of nuclear translocation of angiogenin in HUVE cells."
sparser
"Since the 31RRR33 residues are known to play a pivotal role in the nuclear translocation of ANG, we predicted that a decrease in SASA due to the local folding and close packing of 31RRR33 residues originated due to the replacement of hydrophilic Arg33 to hydrophobic Trp33 would probably lead to the loss of nuclear translocation activity in R33W variant."
sparser
"Treatment of KSHV-infected cell supernatants with antiangiogenin antibodies significantly inhibited endothelial tube formation, and inhibition of nuclear translocation of angiogenin also blocked the expression of KSHV-induced vascular endothelial growth factor C. Collectively, these results strongly suggest that by increasing infected endothelial cell 45S rRNA synthesis, proliferation, migration, and angiogenesis, KSHV-induced angiogenin could be playing a pivotal role in the pathogenesis of KSHV infection, including a contribution to the angioproliferative nature of KS lesions."