Evidence map›Paper›PMID 38038247›Full record

ArticleNucleic acids research2024

Interaction of histone H4 with Cse4 facilitates conformational changes in Cse4 for its sumoylation and mislocalization.

Kentaro Ohkuni, Wei-Chun Au, Amira Z Kazi, Mark Villamil, Peter Kaiser, Munira A Basrai

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
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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

6 authors at 2 institutions in 1 country.

Kentaro OhkuniGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Wei-Chun AuGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Amira Z KaziGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Mark VillamilDepartment of Biological Chemistry, School of Medicine, Center for Epigenetics and Metabolism, Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92697-1700, USA.
Peter KaiserDepartment of Biological Chemistry, School of Medicine, Center for Epigenetics and Metabolism, Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92697-1700, USA.
Munira A BasraiGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0003-0628-8052
National Institutes of Health · USUniversity of California, Irvine · US

Funding

Molecular Determinants of Chromosome Transmission and Cell Cycle RegulationZIABC010822 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BASRAI, MUNIRA · 2009 to 2025
$29.2M
Ubiquitin and Metabolite SignalingR35GM148350 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Peter Kaiser · 2023 to 2026
$2.7M
NIGMS NIH HHS R35 GM148350NIH HHS R35GM148350
6 · The paper itself

Abstract

Mislocalization of overexpressed CENP-A (Cse4 in budding yeast, Cnp1 in fission yeast, CID in flies) contributes to chromosomal instability (CIN) in yeasts, flies, and human cells. Mislocalization of CENP-A is observed in many cancers and this correlates with poor prognosis. Structural mechanisms that contribute to mislocalization of CENP-A are poorly defined. Here, we show that interaction of histone H4 with Cse4 facilitates an in vivo conformational change in Cse4 promoting its mislocalization in budding yeast. We determined that Cse4 Y193A mutant exhibits reduced sumoylation, mislocalization, interaction with histone H4, and lethality in psh1Δ and cdc48-3 strains; all these phenotypes are suppressed by increased gene dosage of histone H4. We developed a new in vivo approach, antibody accessibility (AA) assay, to examine the conformation of Cse4. AA assay showed that wild-type Cse4 with histone H4 is in an 'open' state, while Cse4 Y193A predominantly exhibits a 'closed' state. Increased gene dosage of histone H4 contributes to a shift of Cse4 Y193A to an 'open' state with enhanced sumoylation and mislocalization. We provide molecular insights into how Cse4-H4 interaction changes the conformational state of Cse4 in vivo. These studies advance our understanding for mechanisms that promote mislocalization of CENP-A in human cancers.

Indexed as

Chromosomal Proteins, Non-HistoneHistonesSaccharomyces cerevisiae ProteinsCentromereCentromere Protein ADNA-Binding ProteinsHumansNeoplasmsSaccharomyces cerevisiaeSumoylationCentromere Protein AChromosomal Proteins, Non-HistoneCSE4 protein, S cerevisiaeDNA-Binding ProteinsHistonesSaccharomyces cerevisiae Proteins

Identifiers

PMID38038247
PMCPMC10810195
OpenAlexW4389242779

What OpenQuestion holds

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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.