Evidence map›Paper›PMID 24771851›Full record

Trial reportJournal of immunology (Baltimore, Md. : 1950)2014

Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins.

Marshall P Thomas, Jennifer Whangbo, Geoffrey McCrossan, Aaron J Deutsch, Kimberly Martinod, Michael Walch, Judy Lieberman

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

27 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
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  3. Causal Role for Neutrophil Elastase in Thoracic Aortic Dissection in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2023
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  15. Caspase-7 uses RNA to enhance proteolysis of poly(ADP-ribose) polymerase 1 and other RNA-binding proteins.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  16. Article
  17. A Flow Cytometry-Based Assay for High-Throughput Detection and Quantification of Neutrophil Extracellular Traps in Mixed Cell Populations.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2019
    Article
  18. Review
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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

7 authors at 4 institutions in 1 country.

Marshall P ThomasProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115;Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA 02215; andDepartment of Pediatrics, Harvard Medical School, Boston, MA 02115.
Jennifer WhangboProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115;Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA 02215; andDepartment of Pediatrics, Harvard Medical School, Boston, MA 02115 judy.lieberman@childrens.harvard.edu jennifer.whangbo@childrens.harvard.edu.
Geoffrey McCrossanProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115;Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA 02215; andDepartment of Pediatrics, Harvard Medical School, Boston, MA 02115.
Aaron J DeutschProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115;Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA 02215; andDepartment of Pediatrics, Harvard Medical School, Boston, MA 02115.
Kimberly MartinodProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115;Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA 02215; andDepartment of Pediatrics, Harvard Medical School, Boston, MA 02115.
Michael WalchProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115;Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA 02215; andDepartment of Pediatrics, Harvard Medical School, Boston, MA 02115.
Judy LiebermanProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115;Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA 02215; andDepartment of Pediatrics, Harvard Medical School, Boston, MA 02115 judy.lieberman@childrens.harvard.edu jennifer.whangbo@childrens.harvard.edu.
Boston Children's Hospital · USBoston Children's Museum · USBoston Medical Center · USHarvard University · US

Funding

Granzyme a Pathway of CTL-Mediated Cell DeathR01AI045587 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI LIEBERMAN, JUDY · 1999 to 2008
$4.4M
Regulation of Systemic RNA Interference in the Nematode C. elegansK08HL094460 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI WHANGBO, JENNIFER SUNG · 2009 to 2013
$662k
Granzyme A Pathway of CTL-Mediated Cell DeathR56AI045587 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI LIEBERMAN, JUDY · 2010 to 2010
$525k
NHLBI NIH HHS HL094460NHLBI NIH HHS K08 HL094460NIAID NIH HHS AI45587NIAID NIH HHS R01 AI045587NIAID NIH HHS R56 AI045587
6 · The paper itself

Abstract

Killer lymphocyte granzyme (Gzm) serine proteases induce apoptosis of pathogen-infected cells and tumor cells. Many known Gzm substrates are nucleic acid binding proteins, and the Gzms accumulate in the target cell nucleus by an unknown mechanism. In this study, we show that human Gzms bind to DNA and RNA with nanomolar affinity. Gzms cleave their substrates most efficiently when both are bound to nucleic acids. RNase treatment of cell lysates reduces Gzm cleavage of RNA binding protein targets, whereas adding RNA to recombinant RNA binding protein substrates increases in vitro cleavage. Binding to nucleic acids also influences Gzm trafficking within target cells. Preincubation with competitor DNA and DNase treatment both reduce Gzm nuclear localization. The Gzms are closely related to neutrophil proteases, including neutrophil elastase (NE) and cathepsin G. During neutrophil activation, NE translocates to the nucleus to initiate DNA extrusion into neutrophil extracellular traps, which bind NE and cathepsin G. These myeloid cell proteases, but not digestive serine proteases, also bind DNA strongly and localize to nuclei and neutrophil extracellular traps in a DNA-dependent manner. Thus, high-affinity nucleic acid binding is a conserved and functionally important property specific to leukocyte serine proteases. Furthermore, nucleic acid binding provides an elegant and simple mechanism to confer specificity of these proteases for cleavage of nucleic acid binding protein substrates that play essential roles in cellular gene expression and cell proliferation.

Indexed as

ProteolysisActive Transport, Cell NucleusCell NucleusDNADNA-Binding ProteinsFemaleGranzymesHEK293 CellsHumansMaleNeutrophilsRNARNA-Binding ProteinsDNADNA-Binding ProteinsGranzymesRNARNA-Binding Proteins

Identifiers

PMID24771851
PMCPMC4041364
OpenAlexW2149026115

What OpenQuestion holds

Textmetadata
LicenceTDM
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.