Evidence map›Paper›PMID 34103528›Full record

ArticleNature communications2021

PRMT5-mediated arginine methylation activates AKT kinase to govern tumorigenesis.

Shasha Yin, Liu Liu, Charles Brobbey, Viswanathan Palanisamy, Lauren E Ball, Shaun K Olsen, Michael C Ostrowski, Wenjian Gan

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
4.2field-weighted citation impact, top 4% 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

64 citing papers in PubMed, 83 citations in OpenAlex.

  1. Article
  2. Review
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  5. Article
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  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. MTA-Cooperative PRMT5 Inhibitors Are Efficacious in MTAP-Deleted Malignant Peripheral Nerve Sheath Tumor Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  13. Article
  14. A Further Case for Targeting PRMT5 and the ERK1/2 and PI3K Pathways in CRC.International journal of molecular sciences · 2025
    Article
  15. Article
  16. Zinc Alleviates Gut Barrier Dysfunction by Promoting the Methylation of AKT.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  17. Review
  18. Article
  19. AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025
    Review
  20. mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article

4 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 1 country.

Shasha Yin *Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Liu Liu *Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Charles BrobbeyDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Viswanathan PalanisamyDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.ORCID http://orcid.org/0000-0001-5128-2878
Lauren E BallDepartment of Cell and Molecular Pharmacology, and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA.
Shaun K OlsenDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-1265-7101
Michael C OstrowskiDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.ORCID http://orcid.org/0000-0003-2948-6297
Wenjian GanDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA. ganw@musc.edu.ORCID http://orcid.org/0000-0001-7599-5020
Medical University of South Carolina · USThe University of Texas Health Science Center at San Antonio · US

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND N. DUBOIS · 2009 to 2026
$42.7M
SOUTH CAROLINA COBRE IN OXIDANTS, REDOX BALANCE AND STRESS SIGNALINGP20GM103542 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI TEW, KENNETH D. · 2012 to 2020
$20.2M
The role of SMAD1 and SATB2 in colon patterningP20GM130457 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI STEPHEN A DUNCAN · 2020 to 2026
$18.7M
Proteomics CoreP30DK123704 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DON C. ROCKEY · 2020 to 2026
$8.8M
Structural Biology of the Ubiquitin Conjugation SystemR01GM115568 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI OLSEN, SHAUN · 2015 to 2023
$2.7M
Structure and Function of the Essential Cell Cycle Regulator Cdc34R01GM128731 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Shaun Olsen · 2019 to 2026
$2.5M
Orbitrap Fusion Lumos ETD Mass SpectrometerS10OD025126 · OD · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BALL, LAUREN ELIZABETH · 2018 to 2018
$991k
Elucidating Novel Akt Regulatory Mechanisms to Overcome Akt-mediated Therapeutic Resistance in Breast CancerR00CA207867 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI GAN, WENJIAN · 2019 to 2021
$747k
NCI NIH HHS P30 CA138313NCI NIH HHS R00 CA207867NIDDK NIH HHS P30 DK123704NIGMS NIH HHS P20 GM103542NIGMS NIH HHS P20 GM130457NIGMS NIH HHS R01 GM115568NIGMS NIH HHS R01 GM128731NIH HHS S10 OD025126
6 · The paper itself

Abstract

AKT is involved in a number of key cellular processes including cell proliferation, apoptosis and metabolism. Hyperactivation of AKT is associated with many pathological conditions, particularly cancers. Emerging evidence indicates that arginine methylation is involved in modulating AKT signaling pathway. However, whether and how arginine methylation directly regulates AKT kinase activity remain unknown. Here we report that protein arginine methyltransferase 5 (PRMT5), but not other PRMTs, promotes AKT activation by catalyzing symmetric dimethylation of AKT1 at arginine 391 (R391). Mechanistically, AKT1-R391 methylation cooperates with phosphatidylinositol 3,4,5 trisphosphate (PIP3) to relieve the pleckstrin homology (PH)-in conformation, leading to AKT1 membrane translocation and subsequent activation by phosphoinositide-dependent kinase-1 (PDK1) and the mechanistic target of rapamycin complex 2 (mTORC2). As a result, deficiency in AKT1-R391 methylation significantly suppresses AKT1 kinase activity and tumorigenesis. Lastly, we show that PRMT5 inhibitor synergizes with AKT inhibitor or chemotherapeutic drugs to enhance cell death. Altogether, our study suggests that R391 methylation is an important step for AKT activation and its oncogenic function.

Indexed as

AnimalsAntineoplastic AgentsArginineBiocatalysisBreast NeoplasmsCarcinogenesisCell Line, TumorCell MembraneCell ProliferationEnzyme ActivationFemaleHEK293 CellsHumansMethylationMiceMice, NudeAntineoplastic AgentsArgininePDK1 protein, humanPRMT5 protein, humanProtein-Arginine N-MethyltransferasesProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPyruvate Dehydrogenase Acetyl-Transferring KinaseRNA, Small Interfering

Identifiers

PMID34103528
PMCPMC8187744
OpenAlexW3167892857

What OpenQuestion holds

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LicenceCC BY
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.