Evidence map›Paper›PMID 32366200›Full record

ArticleCirculation research2020

The Calcineurin-TFEB-p62 Pathway Mediates the Activation of Cardiac Macroautophagy by Proteasomal Malfunction.

Bo Pan, Jie Li, Nirmal Parajuli, Zongwen Tian, Penglong Wu, Megan T Lewno, Jianqiu Zou, Wenjuan Wang, Lynn Bedford, R John Mayer and 5 more

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

Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 2 pooled it
12.2field-weighted citation impact, top 1% 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

74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 136 citations in OpenAlex.

  1. Gene expression regulation by CaCellular & molecular biology letters · 2026
    Pooled it
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  3. Article
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  6. Review
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  8. Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026
    Review
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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 4 countries.

Bo Pan *From the Division of Basic Biomedical Sciences, University of South Dakota, Sanford School of Medicine, Vermillion (B.P., J. Li, N.P., Z.T., P.W., M.T.L., H.S., X.W.).
Jie Li *From the Division of Basic Biomedical Sciences, University of South Dakota, Sanford School of Medicine, Vermillion (B.P., J. Li, N.P., Z.T., P.W., M.T.L., H.S., X.W.).
Nirmal Parajuli *From the Division of Basic Biomedical Sciences, University of South Dakota, Sanford School of Medicine, Vermillion (B.P., J. Li, N.P., Z.T., P.W., M.T.L., H.S., X.W.).
Zongwen Tian *From the Division of Basic Biomedical Sciences, University of South Dakota, Sanford School of Medicine, Vermillion (B.P., J. Li, N.P., Z.T., P.W., M.T.L., H.S., X.W.).
Penglong Wu *From the Division of Basic Biomedical Sciences, University of South Dakota, Sanford School of Medicine, Vermillion (B.P., J. Li, N.P., Z.T., P.W., M.T.L., H.S., X.W.).
Megan T LewnoFrom the Division of Basic Biomedical Sciences, University of South Dakota, Sanford School of Medicine, Vermillion (B.P., J. Li, N.P., Z.T., P.W., M.T.L., H.S., X.W.).
Jianqiu ZouVascular Biology Center and Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University (J. Li, J.Z., W.W., H.S.).
Wenjuan WangVascular Biology Center and Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University (J. Li, J.Z., W.W., H.S.).
Lynn BedfordSchool of Life Sciences, University of Nottingham, United Kingdom (L.B.).
R John MayerThe University of Nottingham Medical School, Queen's Medical Centre, United Kingdom (R.J.M.).
Jing FangDepartment of Drug Discovery and Biomedical Sciences (J.F.), University of South Carolina College of Pharmacy, Columbia.
Jinbao LiuGuangzhou Institute of Oncology, Tumor Hospital, Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangdong, China (P.W., W.W., J. Liu).
Taixing CuiDepartment of Anatomy and Cell Biology (T.C.), University of South Carolina College of Pharmacy, Columbia.
Huabo SuFrom the Division of Basic Biomedical Sciences, University of South Dakota, Sanford School of Medicine, Vermillion (B.P., J. Li, N.P., Z.T., P.W., M.T.L., H.S., X.W.).
Xuejun WangFrom the Division of Basic Biomedical Sciences, University of South Dakota, Sanford School of Medicine, Vermillion (B.P., J. Li, N.P., Z.T., P.W., M.T.L., H.S., X.W.).
University of South Dakota · USAugusta University · USUniversity of Nottingham · GBUniversity of South Carolina · USState Key Laboratory of Respiratory Disease · CN

Funding

Ubiquitin receptors and cardiac proteotoxicityR01HL072166 · NHLBI · UNIVERSITY OF SOUTH DAKOTA · PI WANG, XUEJUN · 2003 to 2023
$6.9M
The COP9 SIgnalosome in the HeartR01HL085629 · NHLBI · UNIVERSITY OF SOUTH DAKOTA · PI WANG, XUEJUN · 2006 to 2019
$4.7M
Neddylation and cardiac protein quality controlR01HL124248 · NHLBI · AUGUSTA UNIVERSITY · PI SU, HUABO · 2014 to 2024
$4.1M
Wrestling stress: role of ufm1 modification in pathological cardiac remodelingR01HL146807 · NHLBI · AUGUSTA UNIVERSITY · PI Jie Li · 2020 to 2026
$2.7M
The NRF2-p62 Axis in the Cross-Talk between Proteasomal and Lysosomal DegradationR01HL131667 · NHLBI · UNIVERSITY OF SOUTH DAKOTA · PI CUI, TAIXING, WANG, XUEJUN · 2017 to 2020
$1.4M
NHLBI NIH HHS R01 HL072166NHLBI NIH HHS R01 HL085629NHLBI NIH HHS R01 HL124248NHLBI NIH HHS R01 HL131667NHLBI NIH HHS R01 HL146807
6 · The paper itself

Abstract

rationaleThe ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway are pivotal to proteostasis. Targeting these pathways is emerging as an attractive strategy for treating cancer. However, a significant proportion of patients who receive a proteasome inhibitor-containing regime show cardiotoxicity. Moreover, UPS and autophagic-lysosomal pathway defects are implicated in cardiac pathogenesis. Hence, a better understanding of the cross-talk between the 2 catabolic pathways will help advance cardiac pathophysiology and medicine.

objectiveSystemic proteasome inhibition (PSMI) was shown to increase p62/SQSTM1 expression and induce myocardial macroautophagy. Here we investigate how proteasome malfunction activates cardiac autophagic-lysosomal pathway. METHODS AND

resultsMyocardial macroautophagy, TFEB (transcription factor EB) expression and activity, and p62 expression were markedly increased in mice with either cardiomyocyte-restricted ablation of

conclusions(1) The activation of cardiac macroautophagy by proteasomal malfunction is mediated by the Mocln1-calcineurin-TFEB-p62 pathway; (2) p62 unexpectedly exerts a feed-forward effect on TFEB activation by proteasome malfunction; and (3) targeting the Mcoln1 (mucolipin1)-calcineurin-TFEB-p62 pathway may provide new means to intervene cardiac autophagic-lysosomal pathway activation during proteasome malfunction.

Indexed as

AnimalsAntineoplastic AgentsATPases Associated with Diverse Cellular ActivitiesBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBortezomibCalcineurinCalcineurin InhibitorsHypertrophy, Left VentricularLysosomesMacroautophagyMiceMyocytes, CardiacProteasome Endopeptidase ComplexProteasome InhibitorsProteostasisRatsAntineoplastic AgentsATPases Associated with Diverse Cellular ActivitiesBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBortezomibCalcineurinCalcineurin InhibitorsMcoln1 protein, mouseProteasome Endopeptidase ComplexProteasome InhibitorsRNA, Small InterferingSequestosome-1 ProteinSqstm1 protein, mouseTcfeb protein, mouseTransient Receptor Potential ChannelsUbiquitinautophagycalcineurincardiotoxicityproteasome inhibitorsequestosome-1TFEB protein, ratubiquitin

Identifiers

PMID32366200
PMCPMC7416491
OpenAlexW3022725247

What OpenQuestion holds

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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.