Evidence map›Paper›PMID 29477841›Full record

ArticleBiochemical and biophysical research communications2018

ZSCAN4 is negatively regulated by the ubiquitin-proteasome system and the E3 ubiquitin ligase RNF20.

Benjamin A Portney, Raju Khatri, W Alex Meltzer, Jennifer M Mariano, Michal Zalzman

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

Article in Biochemical and biophysical research communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.5field-weighted citation impact, top 38% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Reprogramming Chromosome Ends by Functional Histone Acetylation.International journal of molecular sciences · 2024
    Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. The Role of Ubiquitination and SUMOylation in Telomere Biology.Current issues in molecular biology · 2020
    Review
  9. Review
  10. 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

5 authors at 1 institution in 1 country.

Benjamin A PortneyDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Raju KhatriDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
W Alex MeltzerDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Jennifer M MarianoDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Michal ZalzmanDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene and Stewart Greenbaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA; The Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: MZalzman@som.umaryland.edu.
University of Maryland, Baltimore · US

Funding

Enhancing the potency of aged adult stem cells for tissue reconstructionR01AR070819 · NIAMS · UNIVERSITY OF MARYLAND BALTIMORE · PI ZALZMAN, MICHAL · 2017 to 2021
$1.7M
A Novel Cell Therapy Approach to Augment Regeneration in Neurodegenerative DiseaseR21NS095088 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI ZALZMAN, MICHAL · 2017 to 2018
$425k
NIAMS NIH HHS R01 AR070819NINDS NIH HHS R21 NS095088
6 · The paper itself

Abstract

Zscan4 is an early embryonic gene cluster expressed in mouse embryonic stem and induced pluripotent stem cells where it plays critical roles in genomic stability, telomere maintenance, and pluripotency. Zscan4 expression is transient, and characterized by infrequent high expression peaks that are quickly down-regulated, suggesting its expression is tightly controlled. However, little is known about the protein degradation pathway responsible for regulating the human ZSCAN4 protein levels. In this study we determine for the first time the ZSCAN4 protein half-life and degradation pathway, including key factors involved in the process, responsible for the regulation of ZSCAN4 stability. We demonstrate lysine 48 specific polyubiquitination and subsequent proteasome dependent degradation of ZSCAN4, which may explain how this key factor is efficiently cleared from the cells. Importantly, our data indicate an interaction between ZSCAN4 and the E3 ubiquitin ligase RNF20. Moreover, our results show that RNF20 depletion by gene knockdown does not affect ZSCAN4 transcription levels, but instead results in increased ZSCAN4 protein levels. Further, RNF20 depletion stabilizes the ZSCAN4 protein half-life, suggesting that RNF20 negatively regulates ZSCAN4 stability. Due to the significant cellular functions of ZSCAN4, our results have important implications in telomere regulation, stem cell biology, and cancer.

Indexed as

Cell LineDNA-Binding ProteinsHalf-LifeHumansLysinePolyubiquitinProteasome Endopeptidase ComplexProtein StabilityProteolysisTranscription FactorsUbiquitinUbiquitinationUbiquitin-Protein LigasesDNA-Binding ProteinsLysinePolyubiquitinProteasome Endopeptidase ComplexRNF20 protein, humanTranscription FactorsUbiquitinUbiquitin-Protein LigasesZSCAN4 protein, humanCancerLysine-48 ubiquitinationProteasomeRNF20Stem cellsTelomeresZSCAN4

Identifiers

PMID29477841
PMCPMC5928792
OpenAlexW2792104770

What OpenQuestion 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 OpenQuestion graph.