Evidence map›Paper›PMID 35490179›Full record

ArticleCell death & disease2022

Deubiquitylase OTUD3 prevents Parkinson's disease through stabilizing iron regulatory protein 2.

Fengju Jia, Hongchang Li, Qian Jiao, Chaonan Li, Lin Fu, Chunping Cui, Hong Jiang, Lingqiang Zhang

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

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

26 citing papers in PubMed, 40 citations in OpenAlex.

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  16. Research progress in deubiquitinase OTUD3.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024
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  18. A Plant Model ofApplied biosciences · 2024
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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

8 authors at 2 institutions in 1 country.

Fengju Jia *Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, Medical College of Qingdao University, Qingdao, 266071, China.
Hongchang Li *State Key Laboratory of Proteomics, National Center of Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 100850, China.ORCID 0000-0003-2107-4925
Qian JiaoDepartment of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, Medical College of Qingdao University, Qingdao, 266071, China.
Chaonan LiDepartment of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, Medical College of Qingdao University, Qingdao, 266071, China.
Lin FuDepartment of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, Medical College of Qingdao University, Qingdao, 266071, China.
Chunping CuiState Key Laboratory of Proteomics, National Center of Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 100850, China.ORCID 0000-0003-0251-3259
Hong JiangDepartment of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, Medical College of Qingdao University, Qingdao, 266071, China. hongjiang@qdu.edu.cn.ORCID 0000-0003-1524-7519
Lingqiang ZhangState Key Laboratory of Proteomics, National Center of Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 100850, China. zhanglq@nic.bmi.ac.cn.ORCID 0000-0002-9795-2141
Qingdao University · CNBeijing Proteome Research Center · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Iron deposits are neuropathological hallmark of Parkinson's disease (PD). Iron regulatory protein 2 (IRP2) is a key factor in regulating brain iron homeostasis. Although two ubiquitin ligases that promote IRP2 degradation have been identified, the deubiquitylase for stabilization of IRP2 in PD remains undefined. Here, we report OTUD3 (OTU domain-containing protein 3) functions as a deubiquitylase for IRP2, interacts with IRP2 in the cytoplasm, de-polyubiquitylates, and stabilizes IRP2 protein in an iron-independent manner. Depletion of OTUD3 results in a disorder of iron metabolism. OTUD3 knockout mice display nigral iron accumulation, motor deficits, and nigrostriatal dopaminergic neurodegeneration, which resembles the pathology of PD. Consistently, decreased levels of OTUD3 are detected in transgenic PD mice expressing A53T mutant of human α-synuclein. Five single nucleotide polymorphism mutations of OTUD3 are present in cases of sporadic PD or controls, although no significant associations of OTUD3 SNPs with sporadic PD are detected. Taken together, these findings demonstrate that OTUD3 is a bona fide deubiquitylase for IRP2 and plays a critical role in the nigral iron deposits in PD.

Indexed as

Parkinson DiseaseAnimalsIronIron Regulatory Protein 2MiceMice, KnockoutMice, TransgenicSubstantia NigraUbiquitin-Specific ProteasesIreb2 protein, mouseIronIron Regulatory Protein 2Otud3 protein, mouseUbiquitin-Specific Proteases

Identifiers

PMID35490179
PMCPMC9056525
OpenAlexW4225147143

What OpenQuestion holds

Textmetadata
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.