ArticleInvestigational new drugs2011
The nuclear transport capacity of a human-pancreatic ribonuclease variant is critical for its cytotoxicity.
Article in Investigational new drugs, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells.Cancers · 2021Article
- The Selectivity for Tumor Cells of Nuclear-Directed Cytotoxic RNases Is Mediated by the Nuclear/Cytoplasmic Distribution of p27Molecules (Basel, Switzerland) · 2021Article
- Construction of Highly Stable Cytotoxic Nuclear-Directed Ribonucleases.Molecules (Basel, Switzerland) · 2018Article
- Activating transcription factor 3 is crucial for antitumor activity and to strengthen the antiviral properties of Onconase.Oncotarget · 2017Article
- A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells.Oncotarget · 2016Article
- Transcriptional repression of RUNX2 is associated with aggressive clinicopathological outcomes, whereas nuclear location of the protein is related to metastasis in prostate cancer.Prostate cancer and prostatic diseases · 2012Article
- A cytotoxic ribonuclease reduces the expression level of P-glycoprotein in multidrug-resistant cell lines.Investigational new drugs · 2012Article
- Rational design and evaluation of mammalian ribonuclease cytotoxins.Methods in enzymology · 2012Article
- A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation.BMC cancer · 2011Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously described a human pancreatic-ribonuclease variant, named PE5, which carries a non-contiguous extended bipartite nuclear localization signal. This signal comprises residues from at least three regions of the protein. We postulated that the introduction of this signal in the ribonuclease provides it with cytotoxic activity because although the variant poorly evades the ribonuclease inhibitor in vitro, it is routed to the nucleus, which is devoid of the inhibitor. In this work, we have investigated the relationship between the cytotoxicity produced by PE5 and its ability to reach the nucleus. First, we show that this enzyme, when incubated with HeLa cells, specifically cleaves nuclear RNA while it leaves cytoplasmic RNA unaffected. On the other hand, we have created new variants in which the residues of the nuclear localization signal that are important for the nuclear transport have been replaced. As expected, the individual changes produce a significant decrease in the cytotoxicity of the resulting variants. We conclude that the nuclear transport of PE5 is critical for its cytotoxicity. Therefore, routing a ribonuclease to the nucleus is an alternative strategy to endow it with cytotoxic activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.