Evidence map›Paper›PMID 31329620›Full record

ArticlePloS one2019

Cullin-4B E3 ubiquitin ligase mediates Apaf-1 ubiquitination to regulate caspase-9 activity.

Eri Ohta, Masanori Itoh, Masashi Ueda, Yoko Hida, Miao-Xing Wang, Miki Hayakawa-Ogura, Shimo Li, Emika Nishida, Kazunori Ohta, Tana and 8 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. 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
0.3field-weighted citation impact, top 44% 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, 9 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. 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

18 authors at 2 institutions in 1 country.

Eri OhtaDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Masanori ItohDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Masashi UedaDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Yoko HidaDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Miao-Xing WangDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Miki Hayakawa-OguraDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Shimo LiDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Emika NishidaDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Kazunori OhtaDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
TanaDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Saiful IslamDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Kiyomi NakagawaDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Tomomi SunayamaDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Huayue ChenDepartment of Anatomy School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Fukuoka, Japan.
So HirataDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Masashi EndoDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Yoya OhnoDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.ORCID 0000-0001-6777-4252
Toshiyuki NakagawaDepartment of Neurobiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.ORCID 0000-0001-8415-4119
Gifu University · JPUniversity of Occupational and Environmental Health Japan · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Apoptotic protease-activating factor 1 (Apaf-1) is a component of apoptosome, which regulates caspase-9 activity. In addition to apoptosis, Apaf-1 plays critical roles in the intra-S-phase checkpoint; therefore, impaired expression of Apaf-1 has been demonstrated in chemotherapy-resistant malignant melanoma and nuclear translocation of Apaf-1 has represented a favorable prognosis of patients with non-small cell lung cancer. In contrast, increased levels of Apaf-1 protein are observed in the brain in Huntington's disease. The regulation of Apaf-1 protein is not yet fully understood. In this study, we show that etoposide triggers the interaction of Apaf-1 with Cullin-4B, resulting in enhanced Apaf-1 ubiquitination. Ubiquitinated Apaf-1, which was degraded in healthy cells, binds p62 and forms aggregates in the cytosol. This complex of ubiquitinated Apaf-1 and p62 induces caspase-9 activation following MG132 treatment of HEK293T cells that stably express bcl-xl. These results show that ubiquitinated Apaf-1 may activate caspase-9 under conditions of proteasome impairment.

Indexed as

UbiquitinationApoptotic Protease-Activating Factor 1bcl-X ProteinCaspase 9Cullin ProteinsEnzyme ActivationEtoposideHEK293 CellsHumansLeupeptinsProtein BindingAPAF1 protein, humanApoptotic Protease-Activating Factor 1bcl-X Proteinbenzyloxycarbonylleucyl-leucyl-leucine aldehydeCaspase 9CUL4B protein, humanCullin ProteinsEtoposideLeupeptins

Identifiers

PMID31329620
PMCPMC6645535
OpenAlexW2963444002

What OpenQuestion holds

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LicenceCC BY
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.