Evidence map›Paper›PMID 40687836›Full record

ArticleiScience2025

Engineering a cell-based orthogonal ubiquitin transfer cascade for profiling the substrates of RBR E3 Parkin.

Shuai Fang, Li Zhou, Geng Chen, Jing Zhang, Xiaoyu Wang, In Ho Jeong, Savannah E Jacobs, Bradley R Kossmann, Wei Wei, Shu Liu and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2025. 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
–field-weighted citation impact
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.

  1. Article
  2. Article
  3. Article
  4. UBE4B Mediates Mitophagy via NIPSNAP1 Ubiquitination and NDP52 Recruitment.International journal of molecular sciences · 2026
    Article
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

19 authors.

Shuai FangEngineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Li ZhouDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Geng ChenDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Jing ZhangDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Xiaoyu WangDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
In Ho JeongDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Savannah E JacobsDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Bradley R KossmannDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Wei WeiNeuroscience Institute and Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30302, USA.
Shu LiuDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Geon H JeongDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Yayun XieDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Duc DuongDepatrment of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
Nicholas T SeyfriedDepatrment of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
Ivaylo IvanovDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Angela M MabbNeuroscience Institute and Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30302, USA.
Hiroaki KiyokawaDepartment of Pharmacology, Northwestern University, Chicago, IL 60611, USA.
Bo ZhaoEngineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Jun YinDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.

Funding

Insights into Gordon Holmes syndrome by substrate profiling of Triad3A and Chip using Orthogonal Ubiquitin TransferR21NS116760 · NINDS · GEORGIA STATE UNIVERSITY · PI MABB, ANGELA M, YIN, JUN · 2021 to 2021
$429k
Protein ubiquitination and deubiquitination in neurological disordersR56NS136464 · NINDS · GEORGIA STATE UNIVERSITY · PI MABB, ANGELA M · 2024 to 2024
$390k
NINDS NIH HHS R21 NS116760NINDS NIH HHS R56 NS136464
6 · The paper itself

Abstract

The E3 ubiquitin (UB) ligase Parkin utilizes a Ring-Between-Ring (RBR) domain to mediate UB transfer to substrate proteins, and mutations affecting Parkin catalysis promote cancer and are associated with Parkinson's disease. An essential role of Parkin is to initiate mitophagy by ubiquitinating mitochondrial proteins. Still, it is unclear how Parkin carries out other cellular functions, such as the regulation of the cell cycle, metabolism, and the neuronal synapse. Here, we used phage display to engineer the RBR domain of Parkin and assembled an orthogonal ubiquitin transfer (OUT) cascade to profile Parkin substrates in living cells. Guided by the substrate profile from the OUT screen, we verified a panel of Rab GTPases and CDK5 as Parkin substrates. We also showed mitophagy stimulation enhanced Parkin-mediated ubiquitination of Rab proteins. Our work demonstrates that the OUT cascade can be an empowering tool for identifying Parkin substrates to elucidate its multifaceted cellular functions.

Indexed as

BiochemistryBiomolecular engineeringMethodology in biological sciencesProteinStructural biology

Identifiers

PMID40687836
PMCPMC12271601

What Socratic 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 Socratic graph.