Evidence map›Paper›PMID 34758305›Full record

ArticleCell reports2021

Interplay between protein acetylation and ubiquitination controls MCL1 protein stability.

Kouhei Shimizu, Min Gi, Shugo Suzuki, Brian J North, Asami Watahiki, Satoshi Fukumoto, John M Asara, Fuminori Tokunaga, Wenyi Wei, Hiroyuki Inuzuka

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
2.5field-weighted citation impact, top 9% 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

44 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
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  5. Crotonylation impedes c-Myc oncogenic activity.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  11. Atlas of lysine acetylation in the mouse.bioRxiv : the preprint server for biology · 2026
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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

10 authors at 5 institutions in 2 countries.

Kouhei ShimizuDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Center for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan; Department of Pathobiochemistry, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan. Electronic address: shimizu.kohei@med.osaka-cu.ac.jp.
Min GiDepartment of Molecular Pathology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan; Department of Environmental Risk Assessment, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan.
Shugo SuzukiDepartment of Molecular Pathology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan.
Brian J NorthDepartment of Biomedical Sciences, Creighton University, Omaha, NE 68178, USA.
Asami WatahikiCenter for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
Satoshi FukumotoCenter for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan; Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan; Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Kyushu University Faculty of Dental Science, Fukuoka 812-8582, Japan.
John M AsaraDivision of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Fuminori TokunagaDepartment of Pathobiochemistry, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan.
Wenyi WeiDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: wwei2@bidmc.harvard.edu.
Hiroyuki InuzukaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: hinuzuka@bidmc.harvard.edu.
Beth Israel Deaconess Medical Center · USOsaka City University · JPCreighton University · USKyushu University · JPTohoku University · JP

Funding

Tuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9M
Decoding and Targeting the PI3K-mTOR Signaling Network in CancerR35CA197459 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI BRENDAN D. MANNING · 2015 to 2026
$10.8M
Deciphering the physiological role and interplay between ubiquitination and phosphorylation pathways to guide targeted cancer therapiesR35CA253027 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Wenyi Wei · 2020 to 2026
$6.2M
Novel regulation of PI3K/Akt to direct targeted breast cancer therapiesR01CA177910 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WEI, WENYI · 2013 to 2023
$3.9M
NCI NIH HHS P01 CA120964NCI NIH HHS R01 CA177910NCI NIH HHS R35 CA197459NCI NIH HHS R35 CA253027
6 · The paper itself

Abstract

The anti-apoptotic myeloid cell leukemia 1 (MCL1) protein belongs to the pro-survival BCL2 family and is frequently amplified or elevated in human cancers. MCL1 is highly unstable, with its stability being regulated by phosphorylation and ubiquitination. Here, we identify acetylation as another critical post-translational modification regulating MCL1 protein stability. We demonstrate that the lysine acetyltransferase p300 targets MCL1 at K40 for acetylation, which is counteracted by the deacetylase sirtuin 3 (SIRT3). Mechanistically, acetylation enhances MCL1 interaction with USP9X, resulting in deubiquitination and subsequent MCL1 stabilization. Therefore, ectopic expression of acetylation-mimetic MCL1 promotes apoptosis evasion of cancer cells, enhances colony formation potential, and facilitates xenografted tumor progression. We further demonstrate that elevated MCL1 acetylation sensitizes multiple cancer cells to pharmacological inhibition of USP9X. These findings reveal that acetylation of MCL1 is a critical post-translational modification enhancing its oncogenic function and provide a rationale for developing innovative therapeutic strategies for MCL1-dependent tumors.

Indexed as

Gene Expression Regulation, NeoplasticProtein StabilityUbiquitinationAcetylationAnimalsApoptosisCell ProliferationFemaleHumansMiceMice, Inbred BALB CMice, NudeMyeloid Cell Leukemia Sequence 1 ProteinNeoplasmsp300-CBP-Associated Factorp300-CBP Transcription FactorsMCL1 protein, humanMyeloid Cell Leukemia Sequence 1 Proteinp300-CBP-Associated Factorp300-CBP Transcription FactorsUbiquitin ThiolesteraseUSP9X protein, humanacetylationchemoresistanceMCL1p300protein degradationprotein stabilityubiquitinationUSP9X

Identifiers

PMID34758305
PMCPMC8621139
OpenAlexW3213395539

What Socratic 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 Socratic graph.