Evidence map›Paper›PMID 26208142›Full record

ArticlePloS one2015

A Novel Interaction between FLICE-Associated Huge Protein (FLASH) and E2A Regulates Cell Proliferation and Cellular Senescence via Tumor Necrosis Factor (TNF)-Alpha-p21WAF1/CIP1 Axis.

Takahiro Hirano, Taichi Murakami, Hiroyuki Ono, Akiko Sakurai, Tatsuya Tominaga, Toshikazu Takahashi, Kojiro Nagai, Toshio Doi, Hideharu Abe

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

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 35% 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

3 citing papers in PubMed, 10 citations in OpenAlex.

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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

9 authors at 1 institution in 1 country.

Takahiro HiranoDepartment of Nephrology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Taichi MurakamiDepartment of Nephrology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Hiroyuki OnoDepartment of Nephrology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Akiko SakuraiDepartment of Nephrology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Tatsuya TominagaDepartment of Nephrology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Toshikazu TakahashiDepartment of Nephrology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Kojiro NagaiDepartment of Nephrology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Toshio DoiDepartment of Nephrology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Hideharu AbeDepartment of Nephrology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Tokushima University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysregulation of the cell proliferation has been implicated in the pathophysiology of a number of diseases. Cellular senescence limits proliferation of cancer cells, preventing tumorigenesis and restricting tissue damage. However, the role of cellular senescence in proliferative nephritis has not been determined. The proliferative peak in experimental rat nephritis coincided with a peak in E2A expression in the glomeruli. Meanwhile, E12 (an E2A-encoded transcription factor) did not promote proliferation of Mesangial cells (MCs) by itself. We identified caspase-8-binding protein FLICE-associated huge protein (FLASH) as a novel E2A-binding partner by using a yeast two-hybrid screening. Knockdown of FLASH suppressed proliferation of MCs. This inhibitory effect was partially reversed by the knockdown of E2A. In addition, the knockdown of FLASH induced cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) expression, but did not affect p53 expression. Furthermore, overexpression of E12 and E47 induced p21, but not p53 in MCs, in the absence of FLASH. We also demonstrated that E2A and p21 expression at the peak of proliferation was followed by significant induction of FLASH in mesangial areas in rat proliferative glomerulonephritis. Moreover, we revealed that FLASH negatively regulates cellular senescence via the interaction with E12. We also demonstrated that FLASH is involved in the TNF-α-induced p21 expressions. These results suggest that the functional interaction of E2A and FLASH play an important role in cell proliferation and cellular senescence via regulation of p21 expression in experimental glomerulonephritis.

Indexed as

Cellular SenescenceAnimalsBasic Helix-Loop-Helix ProteinsCalcium-Binding ProteinsCell LineCell ProliferationCyclin-Dependent Kinase Inhibitor p21Gene Expression RegulationMiceProtein BindingRatsRNA InterferenceRNA, Small InterferingTumor Necrosis Factor-alphaBasic Helix-Loop-Helix ProteinsCalcium-Binding ProteinsCasp8ap2 protein, mouseCyclin-Dependent Kinase Inhibitor p21RNA, Small InterferingTumor Necrosis Factor-alpha

Identifiers

PMID26208142
PMCPMC4514670
OpenAlexW1451249889

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.