Evidence map›Paper›PMID 17705507›Full record

ArticleBiochemistry2007

Cytotoxic ribonucleases: the dichotomy of Coulombic forces.

R Jeremy Johnson, Tzu-Yuan Chao, Luke D Lavis, Ronald T Raines

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 49 citations in OpenAlex.

  1. Reductive Methylation: An Alternative to Lysine → Arginine Mutagenesis.Journal of peptide science : an official publication of the European Peptide Society · 2026
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  13. A novel fully human antitumor immunoRNase resistant to the RNase inhibitor.Protein engineering, design & selection : PEDS · 2013
    Article
  14. Interaction of nucleic acids with the glycocalyx.Journal of the American Chemical Society · 2012
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

R Jeremy JohnsonDepartment of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706-1544, USA.
Tzu-Yuan Chao
Luke D Lavis
Ronald T Raines
University of Wisconsin–Madison · US

Funding

RIBONUCLEASES IN CANCER THERAPYR01CA073808 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI RAINES, RONALD T · 1997 to 2024
$7.3M
ACQUISITION OF MASS SPECTROMETER FOR CORE FACILITYS10RR013790 · NCRR · UNIVERSITY OF WISCONSIN MADISON · PI RAINES, RONALD T · 1999 to 1999
–
NCI NIH HHS CA73808NCI NIH HHS R01 CA073808NCRR NIH HHS RR13790NCRR NIH HHS S10 RR013790PHS HHS 08349
6 · The paper itself

Abstract

Cells tightly regulate their contents. Still, nonspecific Coulombic interactions between cationic molecules and anionic membrane components can lead to adventitious endocytosis. Here, we characterize this process in a natural system. To do so, we create variants of human pancreatic ribonuclease (RNase 1) that differ in net molecular charge. By conjugating a small-molecule latent fluorophore to these variants and using flow cytometry, we are able to determine the kinetic mechanism for RNase 1 internalization into live human cells. We find that internalization increases with solution concentration and is not saturable. Internalization also increases with time to a steady-state level, which varies linearly with molecular charge. In contrast, the rate constant for internalization (t1/2 = 2 h) is independent of charge. We conclude that internalization involves an extracellular equilibrium complex between the cationic proteins and abundant anionic cell-surface molecules, followed by rate-limiting internalization. The enhanced internalization of more cationic variants of RNase 1 is, however, countered by their increased affinity for the cytosolic ribonuclease inhibitor protein, which is anionic. Thus, Coulombic forces mediate extracellular and intracellular equilibria in a dichotomous manner that both endangers cells and defends them from the potentially lethal enzymatic activity of ribonucleases.

Indexed as

Biomechanical PhenomenaCell DeathEndocytosisFluorescent DyesHumansK562 CellsKineticsMutant ProteinsProtein Structure, SecondaryRibonuclease, PancreaticFluorescent DyesMutant ProteinsRibonuclease, Pancreatic

Identifiers

PMID17705507
PMCPMC2864629
OpenAlexW1998745985

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.