Evidence map›Paper›PMID 30929559›Full record

ArticleAutophagy2019

GCA links TRAF6-ULK1-dependent autophagy activation in resistant chronic myeloid leukemia.

Seung Hun Han, Sovannarith Korm, Ye Gi Han, Soo-Young Choi, Soo-Hyun Kim, Hee Jin Chung, Kibeom Park, Jae-Young Kim, Kyungjae Myung, Joo-Yong Lee and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 5% 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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.

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  14. Small molecule modulation of p75Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
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  16. m6A demethylase FTO transcriptionally activated by SP1 improves ischemia reperfusion-triggered acute kidney injury by activating Ambra1/ULK1-mediated autophagy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
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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

12 authors at 5 institutions in 1 country.

Seung Hun HanDepartment of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
Sovannarith KormGraduate School of Analytical Science and Technology, Chungnam National University, Daejeon, Republic of Korea.ORCID 0000-0003-2211-2946
Ye Gi HanDepartment of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
Soo-Young ChoiLeukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
Soo-Hyun KimLeukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
Hee Jin ChungDepartment of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
Kibeom ParkDepartment of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
Jae-Young KimGraduate School of Analytical Science and Technology, Chungnam National University, Daejeon, Republic of Korea.
Kyungjae MyungCenter for Genomic Integrity Institute for Basic Science (IBS), Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Joo-Yong LeeGraduate School of Analytical Science and Technology, Chungnam National University, Daejeon, Republic of Korea.ORCID 0000-0003-1049-6006
Hongtae KimCenter for Genomic Integrity Institute for Basic Science (IBS), Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Dong-Wook KimLeukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
Sungkyunkwan University · KRChungnam National University · KRCatholic University of Korea · KRInstitute for Basic Science · KRThe Catholic University of Korea Seoul St. Mary's Hospital · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Imatinib is the first molecularly targeted compound for chronic myeloid leukemia (CML) capable to inhibit BCR-ABL kinase activity. However, recent clinical evidence indicates that a substantial proportion of CML patients exhibit BCR-ABL-dependent or independent resistance to imatinib. Despite the importance of imatinib resistance in CML, the underlying molecular mechanisms of this resistance are largely unknown. Here, we identified GCA (grancalcin) as a critical regulator of imatinib resistance in chronic phase CML via activation of autophagy. Mechanistically, we demonstrated that GCA activates TRAF6 ubiquitin ligase activity to induce Lys63 ubiquitination of ULK1, a crucial regulator of autophagy, resulting in its stabilization and activation. We also highlighted the role of GCA-TRAF6-ULK1 autophagy regulatory axis in imatinib resistance. Our findings represent the basis for novel therapeutic strategies against CML.

Indexed as

AnimalsAntineoplastic AgentsApoptosisAutophagosomesAutophagyAutophagy-Related Protein-1 HomologCalcium-Binding ProteinsCell SurvivalDrug Resistance, NeoplasmFemaleHumansImatinib MesylateIntracellular Signaling Peptides and ProteinsK562 CellsLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukocytes, MononuclearAntineoplastic AgentsAutophagy-Related Protein-1 HomologCalcium-Binding ProteinsGCA protein, humanImatinib MesylateIntracellular Signaling Peptides and ProteinsTifab protein, humanULK1 protein, humanAutophagychronic myeloid leukemia (CML)grancalcin (GCA)imatinib resistanceTRAF6ULK1

Identifiers

PMID30929559
PMCPMC6844495
OpenAlexW2934724413

What OpenQuestion holds

Textmetadata
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.