Evidence map›Paper›PMID 36848235›Full record

ArticleCell reports2023

Protein adduction causes non-mutational inhibition of p53 tumor suppressor.

Ravindran Caspa Gokulan, Kodisundaram Paulrasu, Jamal Azfar, Wael El-Rifai, Jianwen Que, Olivier G Boutaud, Yuguang Ban, Zhen Gao, Monica Garcia Buitrago, Sergey I Dikalov and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2023. 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
3.2field-weighted citation impact, top 8% 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. Signaling pathways and targeted interventions for precancers.Signal transduction and targeted therapy · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Repetitive sulfur dioxide exposure in mice models post-deployment respiratory syndrome.American journal of physiology. Lung cellular and molecular physiology · 2024
    Article
  10. Esophageal adenocarcinoma models: a closer look.Frontiers in molecular biosciences · 2024
    Review
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

11 authors at 4 institutions in 1 country.

Ravindran Caspa GokulanDepartment of Surgery, University of Miami, Miami, FL, USA.
Kodisundaram PaulrasuDepartment of Surgery, University of Miami, Miami, FL, USA.
Jamal AzfarDepartment of Surgery, University of Miami, Miami, FL, USA.
Wael El-RifaiDepartment of Surgery, University of Miami, Miami, FL, USA.
Jianwen QueDepartment of Medicine, Columbia University Medical Center, New York, NY, USA.
Olivier G BoutaudDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Yuguang BanDepartment of Public Health Sciences, University of Miami, Miami, FL, USA.
Zhen GaoDepartment of Public Health Sciences, University of Miami, Miami, FL, USA.
Monica Garcia BuitragoDepartment of Pathology, University of Miami, Miami, FL, USA.
Sergey I DikalovDepartment of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
Alexander I ZaikaDepartment of Surgery, University of Miami, Miami, FL, USA; Department of Veterans Affairs, Miami VA Healthcare System, Miami, FL, USA. Electronic address: axz353@med.miami.edu.
University of Miami · USVanderbilt University Medical Center · USColumbia University Irving Medical Center · USMiami VA Healthcare System · US

Funding

SOX4-Mediated Transcription Program in Esophageal AdenocarcinomaP01CA268991 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WAEL EL-RIFAI · 2022 to 2026
$9.2M
Regulation of the Oncogenic Stress Response in Helicobacter pylori-infected cellsR01CA138833 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALEXANDER I. ZAIKA · 2010 to 2026
$4.3M
Sirtuin 3 Inactivation and SOD2 Acetylation in Vascular Dysfunction and HypertensionR01HL157583 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DIKALOV, SERGEY · 2021 to 2024
$2.4M
Mechanisms of Tumorigenic Transformation of Barretts EsophagusR01CA206564 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ZAIKA, ALEXANDER I. · 2015 to 2019
$1.8M
Targeting Mitochondrial Cyclophilin D in Vascular Oxidative Stress and HypertensionR01HL144943 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DIKALOV, SERGEY · 2019 to 2022
$1.7M
BLRD Research Career Scientist Award ApplicationIK6BX006300 · VA · MIAMI VA HEALTH CARE SYSTEM · PI ZAIKA, ALEXANDER I. · 2023 to 2025
–
Regulation of gastroesophageal reflux-associated tumorigenesisI01BX002115 · VA · VETERANS HEALTH ADMINISTRATION · PI ZAIKA, ALEXANDER I. · 2014 to 2024
–
BLRD VA I01 BX002115BLRD VA IK6 BX003787BLRD VA IK6 BX006300NCI NIH HHS P01 CA268991NCI NIH HHS R01 CA138833NCI NIH HHS R01 CA206564NHLBI NIH HHS R01 HL144943NHLBI NIH HHS R01 HL157583
6 · The paper itself

Abstract

p53 is a key tumor suppressor that is frequently mutated in human tumors. In this study, we investigated how p53 is regulated in precancerous lesions prior to mutations in the p53 gene. Analyzing esophageal cells in conditions of genotoxic stress that promotes development of esophageal adenocarcinoma, we find that p53 protein is adducted with reactive isolevuglandins (isoLGs), products of lipid peroxidation. Modification of p53 protein with isoLGs diminishes its acetylation and binding to the promoters of p53 target genes causing modulation of p53-dependent transcription. It also leads to accumulation of adducted p53 protein in intracellular amyloid-like aggregates that can be inhibited by isoLG scavenger 2-HOBA in vitro and in vivo. Taken together, our studies reveal a posttranslational modification of p53 protein that causes molecular aggregation of p53 protein and its non-mutational inactivation in conditions of DNA damage that may play an important role in human tumorigenesis.

Indexed as

DNA DamageTumor Suppressor Protein p53Amyloidogenic ProteinsHumansLipid PeroxidationMutationAmyloidogenic ProteinsTumor Suppressor Protein p53CP: Canceresophageal cancerHelicobacter pylorip53p73

Identifiers

PMID36848235
PMCPMC9989503
OpenAlexW4317771279

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.