Evidence map›Paper›PMID 31462068›Full record

ArticleCirculation. Genomic and precision medicine2019

LITAF (Lipopolysaccharide-Induced Tumor Necrosis Factor) Regulates Cardiac L-Type Calcium Channels by Modulating NEDD (Neural Precursor Cell Expressed Developmentally Downregulated Protein) 4-1 Ubiquitin Ligase.

Karni S Moshal, Karim Roder, Anatoli Y Kabakov, Andreas A Werdich, David Yi-Eng Chiang, Nilüfer N Turan, An Xie, Tae Yun Kim, Leroy L Cooper, Yichun Lu and 7 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation. Genomic and precision medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.5field-weighted citation impact, top 35% 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

11 citing papers in PubMed, 12 citations in OpenAlex.

  1. Variable expressivity in long QT syndrome type 2 rabbits defines a low threshold for therapeuticAmerican journal of physiology. Heart and circulatory physiology · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Identification and Functional Assessment of Candidate CausalCirculation. Genomic and precision medicine · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Mechanisms and Regulation of Cardiac CaInternational journal of molecular sciences · 2021
    Review
  10. Article
  11. 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

17 authors at 4 institutions in 1 country.

Karni S MoshalCardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence (K.S.M., K.R., A.Y.K., N.N.T., A.X., T.Y.K., Y.L., W.L., D.T., B.-R.C., G.K.).
Karim RoderCardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence (K.S.M., K.R., A.Y.K., N.N.T., A.X., T.Y.K., Y.L., W.L., D.T., B.-R.C., G.K.).
Anatoli Y KabakovCardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence (K.S.M., K.R., A.Y.K., N.N.T., A.X., T.Y.K., Y.L., W.L., D.T., B.-R.C., G.K.).
Andreas A WerdichCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (A.A.W., D.Y.-E.C., C.A.M.).
David Yi-Eng ChiangCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (A.A.W., D.Y.-E.C., C.A.M.).
Nilüfer N TuranCardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence (K.S.M., K.R., A.Y.K., N.N.T., A.X., T.Y.K., Y.L., W.L., D.T., B.-R.C., G.K.).
An XieCardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence (K.S.M., K.R., A.Y.K., N.N.T., A.X., T.Y.K., Y.L., W.L., D.T., B.-R.C., G.K.).
Tae Yun KimCardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence (K.S.M., K.R., A.Y.K., N.N.T., A.X., T.Y.K., Y.L., W.L., D.T., B.-R.C., G.K.).
Leroy L CooperBiology Department, Vassar College, Poughkeepsie, NY (L.L.C).
Yichun LuCardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence (K.S.M., K.R., A.Y.K., N.N.T., A.X., T.Y.K., Y.L., W.L., D.T., B.-R.C., G.K.).
Mingwang ZhongPhysics Department and Center for Interdisciplinary Research in Complex Systems, Northeastern University, Boston, MA (M.Z., A.K.).
Weiyan LiCardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence (K.S.M., K.R., A.Y.K., N.N.T., A.X., T.Y.K., Y.L., W.L., D.T., B.-R.C., G.K.).
Dmitry TerentyevCardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence (K.S.M., K.R., A.Y.K., N.N.T., A.X., T.Y.K., Y.L., W.L., D.T., B.-R.C., G.K.).
Bum-Rak ChoiCardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence (K.S.M., K.R., A.Y.K., N.N.T., A.X., T.Y.K., Y.L., W.L., D.T., B.-R.C., G.K.).
Alain KarmaPhysics Department and Center for Interdisciplinary Research in Complex Systems, Northeastern University, Boston, MA (M.Z., A.K.).
Calum A MacRaeCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (A.A.W., D.Y.-E.C., C.A.M.).
Gideon KorenCardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence (K.S.M., K.R., A.Y.K., N.N.T., A.X., T.Y.K., Y.L., W.L., D.T., B.-R.C., G.K.).
Brown University · USBrigham and Women's Hospital · USNortheastern University · USVassar College · US

Funding

A Multi-Scale Approach to Cardiac Arrhythmia: from the Molecule to the OrganR01HL110791 · NHLBI · RHODE ISLAND HOSPITAL · PI KOREN, GIDEON · 2013 to 2017
$7.3M
Novel Mechanisms of Regulation of SK channels: Implications for Cardiac ArrhythmiaR01HL142588 · NHLBI · OHIO STATE UNIVERSITY · PI TERENTYEV, DMITRY A · 2019 to 2022
$2.4M
Cardiac ubiquitin ligases: regulation and role in modulating cardiac excitation.R01HL134706 · NHLBI · RHODE ISLAND HOSPITAL · PI KOREN, GIDEON · 2017 to 2020
$2.4M
Brown CardioPulmonary Research Training ProgramT32HL094300 · NHLBI · RHODE ISLAND HOSPITAL · PI KOREN, GIDEON · 2008 to 2012
$2.2M
REgulation of Calcium Homeostasis by MyomiRs in Heart FailureR01HL121796 · NHLBI · RHODE ISLAND HOSPITAL · PI TERENTYEV, DMITRY A · 2015 to 2019
$2.0M
The role of dynamic changes in repolarization and calcium transients in Long QT rR01HL096669 · NHLBI · RHODE ISLAND HOSPITAL · PI CHOI, BUM-RAK · 2009 to 2013
$1.9M
Molecular Mechanisms of Stretch-Induced Electrical Remodeling in the HeartR00HL112724 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WERDICH, ANDREAS AUGUSTINUS · 2015 to 2018
$747k
NHLBI NIH HHS R00 HL112724NHLBI NIH HHS R01 HL096669NHLBI NIH HHS R01 HL110791NHLBI NIH HHS R01 HL121796NHLBI NIH HHS R01 HL134706NHLBI NIH HHS R01 HL142588NHLBI NIH HHS T32 HL094300
6 · The paper itself

Abstract

backgroundThe turnover of cardiac ion channels underlying action potential duration is regulated by ubiquitination. Genome-wide association studies of QT interval identified several single-nucleotide polymorphisms located in or near genes involved in protein ubiquitination. A genetic variant upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor) gene prompted us to determine its role in modulating cardiac excitation.

methodsOptical mapping was performed in zebrafish hearts to determine Ca

resultsLITAF knockdown in zebrafish resulted in a robust increase in calcium transients. Overexpressed LITAF in 3-week-old rabbit cardiomyocytes resulted in a decrease in

conclusionsLITAF acts as an adaptor protein promoting NEDD4-1-mediated ubiquitination and subsequent degradation of LTCC, thereby controlling LTCC membrane levels and function and thus cardiac excitation.

Indexed as

AnimalsCalciumCalcium Channels, L-TypeDNA-Binding ProteinsHeartHumansMembrane ProteinsMyocytes, CardiacNedd4 Ubiquitin Protein LigasesNuclear ProteinsRabbitsTranscription FactorsUbiquitinationZebrafishZebrafish ProteinsCalciumCalcium Channels, L-TypeDNA-Binding ProteinsLITAF protein, humanlitaf protein, zebrafishMembrane Proteinsnedd4a protein, zebrafishNedd4 protein, humanNedd4 Ubiquitin Protein LigasesNuclear ProteinsTranscription FactorsZebrafish Proteinsaction potentialcalciumrabbittumor necrosis factorubiquitination

Identifiers

PMID31462068
PMCPMC6750970
OpenAlexW2974928876

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.