Evidence map›Paper›PMID 34415726›Full record

ArticleACS chemical biology2021

A Peptidomimetic Ligand Targeting the Chromodomain of MPP8 Reveals HRP2's Association with the HUSH Complex.

Jarod M Waybright, Sarah E Clinkscales, Kimberly D Barnash, Gabrielle R Budziszewski, Justin M Rectenwald, Anna M Chiarella, Jacqueline L Norris-Drouin, Stephanie H Cholensky, Kenneth H Pearce, Laura E Herring and 3 more

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Chemical tools targeting readers of lysine methylation.Current opinion in chemical biology · 2023
    Review
  9. Article
  10. Virtual Special Issue: Epigenetics 2022.ACS pharmacology & translational science · 2022
    Article
  11. Virtual Special Issue: Epigenetics 2022.ACS medicinal chemistry letters · 2022
    Article
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

13 authors at 1 institution in 1 country.

Jarod M WaybrightCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.ORCID 0000-0002-5226-8231
Sarah E ClinkscalesCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Kimberly D Barnash
Gabrielle R BudziszewskiDepartment of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Justin M RectenwaldDepartment of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Anna M ChiarellaCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Jacqueline L Norris-DrouinCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Stephanie H CholenskyCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Kenneth H PearceCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Laura E HerringUNC Proteomics Core Facility, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.ORCID 0000-0003-4496-7312
Robert K McGintyCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Nathaniel A HathawayCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Lindsey I JamesCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.ORCID 0000-0002-6034-7116
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Molecular Mechanisms of Chromatin RecognitionR35GM133498 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Robert McGinty · 2019 to 2026
$3.3M
POLYCOMB REPRESSIVE COMLEXE AS KEY REGULATORS OF HIV LATENCY AND TARGETS FOR LATENCY REVERSALR61DA047023 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JAMES, LINDSEY INGERMAN · 2018 to 2020
$2.7M
Cancer Epigenetics Training GrantT32CA217824 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WEISSMAN, BERNARD E. · 2017 to 2021
$1.8M
MECHANISM OF HP1-MEDIATED HETEROCHROMATIN ASSEMBLY AND DURABILITY IN LIVE CELLSR01GM118653 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HATHAWAY, NATHANIEL A. · 2017 to 2021
$1.7M
Training in Mechanistic, Interdisciplinary Studies of Biological SystemsT32GM119999 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RAMSDEN, DALE A · 2017 to 2021
$1.2M
Computational and experimental insights into the structure and dynamics of heterochromatinR01GM132299 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HATHAWAY, NATHANIEL A., KIREEV, DMITRI · 2020 to 2023
$1.2M
NCI NIH HHS P30 CA016086NCI NIH HHS T32 CA217824NIDA NIH HHS R61 DA047023NIGMS NIH HHS R01 GM118653NIGMS NIH HHS R01 GM132299NIGMS NIH HHS R35 GM133498NIGMS NIH HHS T32 GM119999
6 · The paper itself

Abstract

The interpretation of histone post-translational modifications (PTMs), specifically lysine methylation, by specific classes of "reader" proteins marks an important aspect of epigenetic control of gene expression. Methyl-lysine (Kme) readers often regulate gene expression patterns through the recognition of a specific Kme PTM while participating in or recruiting large protein complexes that contain enzymatic or chromatin remodeling activity. Understanding the composition of these Kme-reader-containing protein complexes can serve to further our understanding of the biological roles of Kme readers, while small molecule chemical tools can be valuable reagents in interrogating novel protein-protein interactions. Here, we describe our efforts to target the chromodomain of M-phase phosphoprotein 8 (MPP8), a member of the human silencing hub (HUSH) complex and a histone 3 lysine 9 trimethyl (H3K9me3) reader that is vital for heterochromatin formation and has specific roles in cancer metastasis. Utilizing a one-bead, one-compound (OBOC) combinatorial screening approach, we identified UNC5246, a peptidomimetic ligand capable of interacting with the MPP8 chromodomain in the context of the HUSH complex. Additionally, a biotinylated derivative of UNC5246 facilitated chemoproteomics studies which revealed hepatoma-derived growth factor-related protein 2 (HRP2) as a novel protein associated with MPP8. HRP2 was further shown to colocalize with MPP8 at the

Indexed as

Cell Cycle ProteinsFluorescence Resonance Energy TransferHistonesHydrophobic and Hydrophilic InteractionsIntercellular Signaling Peptides and ProteinsLigandsLysineMass SpectrometryMethylationModels, MolecularPeptidomimeticsPhosphoproteinsProtein BindingProtein DomainsProtein Processing, Post-TranslationalProteomicsCell Cycle Proteinshepatoma-derived growth factorHistonesIntercellular Signaling Peptides and ProteinsLigandsLysinePeptidomimeticsPhosphoproteins

Identifiers

PMID34415726
PMCPMC8448959
OpenAlexW3194314664

What OpenQuestion holds

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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 OpenQuestion graph.