Evidence map›Paper›PMID 39135477›Full record

ArticleMolecular and cellular biology2024

β-TrCP-Mediated Proteolysis of Mis18β Prevents Mislocalization of CENP-A and Chromosomal Instability.

Subhash Chandra Sethi, Roshan Lal Shrestha, Vinutha Balachandra, Geetha Durairaj, Wei-Chun Au, Michael Nirula, Tatiana S Karpova, Peter Kaiser, Munira A Basrai

Abstract read
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In one paragraph

Article in Molecular and cellular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Preserving centromere identity: right amounts of CENP-A at the right place and time.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2025
    Review
  5. 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

9 authors.

Subhash Chandra SethiGenetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Roshan Lal ShresthaGenetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Vinutha BalachandraGenetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Geetha DurairajDepartment of Biological Chemistry, School of Medicine, University of California, Irvine, California, USA.
Wei-Chun AuGenetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Michael NirulaGenetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Tatiana S KarpovaLaboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Peter KaiserDepartment of Biological Chemistry, School of Medicine, University of California, Irvine, California, USA.
Munira A BasraiGenetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Funding

Ubiquitin and Metabolite SignalingR35GM148350 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Peter Kaiser · 2023 to 2026
$2.7M
NIGMS NIH HHS R35 GM148350
6 · The paper itself

Abstract

Restricting the localization of evolutionarily conserved histone H3 variant CENP-A to the centromere is essential to prevent chromosomal instability (CIN), an important hallmark of cancers. Overexpressed CENP-A mislocalizes to non-centromeric regions and contributes to CIN in yeast, flies, and human cells. Centromeric localization of CENP-A is facilitated by the interaction of Mis18β with CENP-A specific chaperone HJURP. Cellular levels of Mis18β are regulated by β-transducin repeat containing protein (β-TrCP), an F-box protein of SCF (Skp1, Cullin, F-box) E3-ubiquitin ligase complex. Here, we show that defects in β-TrCP-mediated proteolysis of Mis18β contributes to the mislocalization of endogenous CENP-A and CIN in a triple-negative breast cancer (TNBC) cell line, MDA-MB-231. CENP-A mislocalization in β-TrCP depleted cells is dependent on high levels of Mis18β as depletion of Mis18β suppresses mislocalization of CENP-A in these cells. Consistent with these results, endogenous CENP-A is mislocalized in cells overexpressing Mis18β alone. In summary, our results show that β-TrCP-mediated degradation of Mis18β prevents mislocalization of CENP-A and CIN. We propose that deregulated expression of Mis18β may be one of the key mechanisms that contributes to chromosome segregation defects in cancers.

Indexed as

beta-Transducin Repeat-Containing ProteinsCell Cycle ProteinsCentromere Protein AChromosomal InstabilityChromosomal Proteins, Non-HistoneProteolysisAdaptor Proteins, Signal TransducingAutoantigensCell Line, TumorCentromereDNA-Binding ProteinsHumansAdaptor Proteins, Signal TransducingAutoantigensbeta-Transducin Repeat-Containing ProteinsBTRC protein, humanCell Cycle ProteinsCENPA protein, humanCentromere Protein AChromosomal Proteins, Non-HistoneDNA-Binding ProteinsHJURP protein, humanOIP5 protein, humanCENP-Acentromerechromosomal instabilityE3 ubiquitin ligaseMis18ββ-TrCP

Identifiers

PMID39135477
PMCPMC11486186

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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.