Evidence map›Paper›PMID 30769864›Full record

ArticleCancers2019

A H2AX⁻CARP-1 Interaction Regulates Apoptosis Signaling Following DNA Damage.

Sreeja C Sekhar, Jaganathan Venkatesh, Vino T Cheriyan, Magesh Muthu, Edi Levi, Hadeel Assad, Paul Meister, Vishnu V Undyala, James W Gauld, Arun K Rishi

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. The Anti-Cancer Effect ofAntioxidants (Basel, Switzerland) · 2019
    Article
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

10 authors at 4 institutions in 2 countries.

Sreeja C SekharJohn D. Dingell Veterans Administration Medical Center, Detroit, MI 48201, USA. sreejacsekhar@gmail.com.
Jaganathan VenkateshJohn D. Dingell Veterans Administration Medical Center, Detroit, MI 48201, USA. jaganvibt@gmail.com.
Vino T CheriyanJohn D. Dingell Veterans Administration Medical Center, Detroit, MI 48201, USA. vinorcc@gmail.com.
Magesh MuthuJohn D. Dingell Veterans Administration Medical Center, Detroit, MI 48201, USA. magesh.research@gmail.com.ORCID 0000-0003-3311-8120
Edi LeviJohn D. Dingell Veterans Administration Medical Center, Detroit, MI 48201, USA. Edi.Levi@va.gov.
Hadeel AssadDepartment of Oncology, Karmanos Cancer Institute, Detroit, MI 48201, USA. Assadh@karmanos.org.
Paul MeisterDepartment of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada. meisterp@uwindsor.ca.ORCID 0000-0002-1836-0093
Vishnu V UndyalaCardiovascular Research Institute, School of Medicine, Wayne State University, Detroit, MI 48201, USA. uvreddi@gmail.com.
James W GauldDepartment of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada. gauld@uwindsor.ca.ORCID 0000-0002-2956-9781
Arun K RishiJohn D. Dingell Veterans Administration Medical Center, Detroit, MI 48201, USA. rishia@Karmanos.org.
John D. Dingell VA Medical Center · USUniversity of Windsor · CAThe Barbara Ann Karmanos Cancer Institute · USWayne State University · US

Funding

CARP-1: A Potential Therapeutic Agent for Breast CancerI01BX001164 · VA · JOHN D DINGELL VA MEDICAL CENTER · PI RISHI, ARUN KUMAR · 2012 to 2020
–
BLRD Research Career Scientist Award ApplicationIK6BX004015 · VA · JOHN D DINGELL VA MEDICAL CENTER · PI Arun Kumar Rishi · 2018 to 2026
–
BLRD VA I01 BX001164BLRD VA IK6 BX004015U.S. Department of Veterans Affairs 5I01BX001164-07
6 · The paper itself

Abstract

Cell Cycle and Apoptosis Regulatory Protein (CARP-1/CCAR1) is a peri-nuclear phosphoprotein that regulates apoptosis via chemotherapeutic Adriamycin (doxorubicin) and a novel class of CARP-1 functional mimetic (CFM) compounds. Although Adriamycin causes DNA damage, data from Comet assays revealed that CFM-4.16 also induced DNA damage. Phosphorylation of histone 2AX (γH2AX) protein is involved in regulating DNA damage repair and apoptosis signaling. Adriamycin or CFM-4.16 treatments inhibited cell growth and caused elevated CARP-1 and γH2AX in human breast (HBC) and cervical cancer (HeLa) cells. In fact, a robust nuclear or peri-nuclear co-localization of CARP-1 and γH2AX occurred in cells undergoing apoptosis. Knock-down of CARP-1 diminished γH2AX, their co-localization, and apoptosis in CFM-4.16- or Adriamycin-treated cells. We found that CARP-1 directly binds with H2AX, and H2AX interacted with CARP-1, but not CARP-1 (Δ600⁻652) mutant. Moreover, cells expressing CARP-1 (Δ600⁻652) mutant were resistant to apoptosis, and had diminished levels of γH2AX, when compared with cells expressing wild-type CARP-1. Mutagenesis studies revealed that H2AX residues 1⁻35 harbored a CARP-1-binding epitope, while CARP-1 amino acids 636⁻650 contained an H2AX-interacting epitope. Surface plasmon resonance studies revealed that CARP-1 (636⁻650) peptide bound with H2AX (1⁻35) peptide with a dissociation constant (K

Indexed as

apoptosiscancer cellsCCAR1/CARP-1chemotherapeuticsγH2AX

Identifiers

PMID30769864
PMCPMC6406907
OpenAlexW2911824374

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.