Evidence map›Paper›PMID 32463099›Full record

ArticleBiology of reproduction2020

A cell-based high-content screen identifies isocotoin as a small molecule inhibitor of the meiosis-specific MEIOB-SPATA22 complex†.

Yang Xu, Rong Liu, N Adrian Leu, Lei Zhang, Ilsiya Ibragmova, David C Schultz, P Jeremy Wang

Open access · hybridAbstract read
In one paragraph

Article in Biology of reproduction, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed, 9 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

7 authors at 1 institution in 2 countries.

Yang XuDepartment of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
Rong LiuDepartment of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
N Adrian LeuDepartment of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
Lei ZhangDepartment of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
Ilsiya IbragmovaHigh-Throughput Screening Core, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
David C SchultzHigh-Throughput Screening Core, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
P Jeremy WangDepartment of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
University of Pennsylvania · US

Funding

Regulation of meiosis in miceR35GM118052 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI WANG, PEIJING JEREMY · 2016 to 2020
$2.8M
Targeting the piRNA pathway and meiotic recombination for male contraceptionR01HD084007 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI WANG, PEIJING JEREMY · 2017 to 2019
$840k
Targeting the piRNA pathway and meiotic recombination for male contraceptionU01HD084007 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI WANG, PEIJING JEREMY · 2015 to 2016
$557k
NICHD NIH HHS R01 HD084007NICHD NIH HHS U01 HD084007NIGMS NIH HHS R35 GM118052
6 · The paper itself

Abstract

MEIOB and SPATA22 are meiosis-specific proteins, interact with each other, and are essential for meiotic recombination and fertility. Aspartic acid 383 (D383) in MEIOB is critical for its interaction with SPATA22 in biochemical studies. Here we report that genetic studies validate the requirement of D383 for the function of MEIOB in mice. The MeiobD383A/D383A mice display meiotic arrest due to depletion of both MEIOB and SPATA22 proteins in the testes. We developed a cell-based bimolecular fluorescence complementation (BiFC) assay, in which MEIOB and SPATA22 are fused to split YFP moieties and their co-expression in cultured cells leads to the MEIOB-SPATA22 dimerization and reconstitution of the fluorophore. As expected, the interaction-disrupting D383A substitution results in the absence of YFP fluorescence in the BiFC assay. A high-throughput screen of small molecule libraries identified candidate hit compounds at a rate of 0.7%. Isocotoin, a hit compound from the natural product library, inhibits the MEIOB-SPATA22 interaction and promotes their degradation in HEK293 cells in a dose-dependent manner. Therefore, the BiFC assay can be employed to screen for small molecule inhibitors that disrupt protein-protein interactions or promote degradation of meiosis-specific proteins.

Indexed as

AnimalsCell Cycle ProteinsDNA-Binding ProteinsFertilityHEK293 CellsHumansMaleMeiosisMiceTestisCell Cycle ProteinsDNA-Binding ProteinsMEIOB protein, mouseSPATA22 protein, mouseisocotoinmale contraceptionMEIOBmeiosisSPATA22

Identifiers

PMID32463099
PMCPMC7523692
OpenAlexW3018336098

What OpenQuestion holds

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Registered trials

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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.