Evidence map›Paper›PMID 37905842›Full record

ArticleThe Prostate2024

Inhibition of N-myristoyltransferase activity promotes androgen receptor degradation in prostate cancer.

Omar Awad Alsaidan, Emmanuel Onobun, Chenming Ye, Lei Lou, Zanna Beharry, Zhong-Ru Xie, Iryna Lebedyeva, David Crich, Houjian Cai

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

Article in The Prostate, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 28% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Crosstalk between protein lipidation and ubiquitination in tumor biology.Apoptosis : an international journal on programmed cell death · 2026
    Review
  2. Review
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

9 authors at 3 institutions in 2 countries.

Omar Awad AlsaidanDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia Athens, Athens, Georgia, USA.
Emmanuel OnobunDepartment of Chemistry, Franklin College of Arts and Sciences, University of Georgia Athens, Athens, Georgia, USA.
Chenming YeDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia Athens, Athens, Georgia, USA.
Lei LouSchool of Electrical and Computer Engineering, College of Engineering, University of Georgia Athens, Athens, Georgia, USA.
Zanna BeharryDepartment of Chemical and Physical Sciences, University of the Virgin Islands, Saint Thomas, Virgin Islands, USA.ORCID 0000-0002-3900-8523
Zhong-Ru XieSchool of Electrical and Computer Engineering, College of Engineering, University of Georgia Athens, Athens, Georgia, USA.
Iryna LebedyevaDepartment of Chemistry and Physics, Augusta University, Augusta, Georgia, USA.
David CrichDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia Athens, Athens, Georgia, USA.
Houjian CaiDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia Athens, Athens, Georgia, USA.ORCID 0000-0002-0158-1017
University of Georgia · USAugusta University · USUniversity of the Virgin Islands · VI

Funding

Blocking TMPRSS2 expression for prevention of SARS-CoV-2 infectionR21AI157831 · NIAID · UNIVERSITY OF GEORGIA · PI Houjian Cai · 2023 to 2023
$189k
NCI NIH HHS U01 CA225784NIAID NIH HHS R21 AI157831NIH HHS R21AI157831NIH HHS U01CA225784
6 · The paper itself

Abstract

backgroundEven though prostate cancer (PCa) patients initially respond to androgen deprivation therapy, some will eventually develop castration resistant prostate cancer (CRPC). Androgen receptor (AR) mediated cell signaling is a major driver in the progression of CRPC while only a fraction of PCa becomes AR negative. This study aimed to understand the regulation of AR levels by N-myristoyltransferase in PCa cells.

methodsTwo enantiomers, (1S,2S)- d-NMAPPD and (1R,2R)- d-NMAPPD (LCL4), were characterized by various methods (

results(1R,2R)- d-NMAPPD, but not its enantiomer (1S,2S)- d-NMAPPD, inhibited NMT1 activity and reduced AR protein levels. (1R,2R)-LCL204, a derivative of (1R,2R)- d-NMAPPD, inhibited global protein myristoylation. It also suppressed protein levels, nuclear translocation, and transcriptional activity of AR full-length or variants in PCa cells. This was due to enhanced ubiquitin and proteasome-mediated degradation of AR. Knockdown of NMT1 levels inhibited tumor growth and proliferation of cancer cells.

conclusionInhibitory efficacy on N-myristoyltransferase activity by d-NMAPPD is stereospecific. (1R,2R)-LCL204 reduced global N-myristoylation and androgen receptor protein levels at low micromolar concentrations in prostate cancer cells. pharmacological inhibition of NMT1 enhances ubiquitin-mediated proteasome degradation of AR. This study illustrates a novel function of N-myristoyltransferase and provides a potential strategy for treatment of CRPC.

Indexed as

Prostatic Neoplasms, Castration-ResistantReceptors, AndrogenAcyltransferasesAndrogen AntagonistsAndrogensCell Line, TumorHumansMaleProteasome Endopeptidase ComplexUbiquitinsAcyltransferasesAndrogen AntagonistsAndrogensglycylpeptide N-tetradecanoyltransferaseProteasome Endopeptidase ComplexReceptors, AndrogenUbiquitinsARmyristoylationNMT1prostate cancerubiquitination

Identifiers

PMID37905842
PMCPMC10872856
OpenAlexW4388035633

What Socratic 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 Socratic graph.